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Introduction

Diet, physical activity, and behavioral therapy, pharmacotherapy, medical devices for weight loss, metabolic surgery, 8. obesity management for the treatment of type 2 diabetes: standards of medical care in diabetes—2021.

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American Diabetes Association; 8. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes—2021 . Diabetes Care 1 January 2021; 44 (Supplement_1): S100–S110. https://doi.org/10.2337/dc21-S008

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The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee ( https://doi.org/10.2337/dc21-SPPC ), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction ( https://doi.org/10.2337/dc21-SINT ). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC .

There is strong and consistent evidence that obesity management can delay the progression from prediabetes to type 2 diabetes ( 1 – 5 ) and is highly beneficial in the treatment of type 2 diabetes ( 6 – 17 ). In patients with type 2 diabetes who also have overweight or obesity, modest and sustained weight loss has been shown to improve glycemic control and reduce the need for glucose-lowering medications ( 6 – 8 ). Several studies have demonstrated that in patients with type 2 diabetes and obesity, more intensive dietary energy restriction with very-low-calorie diets can substantially reduce A1C and fasting glucose and promote sustained diabetes remission through at least 2 years ( 10 , 18 – 21 ). The goal of this section is to provide evidence-based recommendations for obesity management, including dietary, behavioral, pharmacologic, and surgical interventions, in patients with type 2 diabetes. This section focuses on obesity management in adults. Further discussion on obesity in older individuals and children can be found in Section 12 “Older Adults” ( https://doi.org/10.2337/dc21-S012 ) and Section 13 “Children and Adolescents” ( https://doi.org/10.2337/dc21-S013 ), respectively.

Recommendations

8.1 Use patient-centered, nonjudgmental language that fosters collaboration between patients and providers, including people-first language (e.g., “person with obesity” rather than “obese person”). E

8.2 Measure height and weight and calculate BMI at annual visits or more frequently. Assess weight trajectory to inform treatment considerations. E

8.3 Based on clinical considerations, such as the presence of comorbid heart failure or significant unexplained weight gain or loss, weight may need to be monitored and evaluated more frequently. B If deterioration of medical status is associated with significant weight gain or loss, inpatient evaluation should be considered, especially focused on associations between medication use, food intake, and glycemic status. E

8.4 Accommodations should be made to provide privacy during weighing. E

A patient-centered communication style that uses inclusive and nonjudgmental language and active listening, elicits patient preferences and beliefs, and assesses potential barriers to care should be used to optimize patient health outcomes and health-related quality of life. Use people-first language (e.g., “person with obesity” rather than “obese person”) to avoid defining patients by their condition ( 22 , 23 , 23a ).

Height and weight should be measured and used to calculate BMI at annual visits or more frequently when appropriate ( 19 ). BMI, calculated as weight in kilograms divided by the square of height in meters (kg/m 2 ), will be calculated automatically by most electronic medical records. Use BMI to document weight status (overweight: BMI 25–29.9 kg/m 2 ; obesity class I: BMI 30–34.9 kg/m 2 ; obesity class II: BMI 35–39.9 kg/m 2 ; obesity class III: BMI ≥40 kg/m 2 ). Note that misclassification can occur, particularly in very muscular or frail individuals. In some populations, notably Asian and Asian American populations, the BMI cut points to define overweight and obesity are lower than in other populations due to differences in body composition and cardiometabolic risk ( Table 8.1 ) ( 24 , 25 ). Clinical considerations, such as the presence of comorbid heart failure or unexplained weight change, may warrant more frequent weight measurement and evaluation ( 26 , 27 ). If weighing is questioned or refused, the practitioner should be mindful of possible prior stigmatizing experiences and query for concerns, and the value of weight monitoring should be explained as a part of the medical evaluation process that helps to inform treatment decisions ( 28 , 29 ). Accommodations should be made to ensure privacy during weighing, particularly for those patients who report or exhibit a high level of weight-related distress or dissatisfaction. Scales should be situated in a private area or room. Weight should be measured and reported nonjudgmentally. Care should be taken to regard a patient’s weight (and weight changes) and BMI as sensitive health information. Additionally, assessing weight gain pattern and trajectory can further inform risk stratification and treatment options ( 30 ). Providers should advise patients with overweight or obesity and those with increasing weight trajectories that, in general, higher BMIs increase the risk of diabetes, cardiovascular disease, and all-cause mortality, as well as other adverse health and quality of life outcomes. Providers should assess readiness to engage in behavioral changes for weight loss and jointly determine behavioral and weight-loss goals and patient-appropriate intervention strategies ( 31 ). Strategies may include dietary changes, physical activity, behavioral therapy, pharmacologic therapy, medical devices, and metabolic surgery ( Table 8.1 ). The latter three strategies may be prescribed for carefully selected patients as adjuncts to dietary changes, physical activity, and behavioral counseling.

Treatment options for overweight and obesity in type 2 diabetes

Recommended cut points for Asian American individuals (expert opinion).

Treatment may be indicated for select motivated patients.

8.5 Diet, physical activity, and behavioral therapy designed to achieve and maintain ≥5% weight loss is recommended for most patients with type 2 diabetes who have overweight or obesity and are ready to achieve weight loss. Greater benefits in control of diabetes and cardiovascular risk may be gained from even greater weight loss. B

8.6 Such interventions should include a high frequency of counseling (≥16 sessions in 6 months) and focus on dietary changes, physical activity, and behavioral strategies to achieve a 500–750 kcal/day energy deficit. A

8.7 An individual's preferences, motivation, and life circumstances should be considered, along with medical status, when weight loss interventions are recommended. C

8.8 Behavioral changes that create an energy deficit, regardless of macronutrient composition, will result in weight loss. Dietary recommendations should be individualized to the patient's preferences and nutritional needs. A

8.9 Evaluate systemic, structural, and socioeconomic factors that may impact dietary patterns and food choices, such as food insecurity and hunger, access to healthful food options, cultural circumstances, and social determinants of health. C

8.10 For patients who achieve short-term weight-loss goals, long-term (≥1 year) weight-maintenance programs are recommended when available. Such programs should, at minimum, provide monthly contact and support, recommend ongoing monitoring of body weight (weekly or more frequently) and other self-monitoring strategies, and encourage high levels of physical activity (200–300 min/week). A

8.11 Short-term dietary intervention using structured, very-low-calorie diets (800–1,000 kcal/day) may be prescribed for carefully selected patients by trained practitioners in medical settings with close monitoring. Long-term, comprehensive weight-maintenance strategies and counseling should be integrated to maintain weight loss. B

Among patients with both type 2 diabetes and overweight or obesity who have inadequate glycemic, blood pressure, and lipid control and/or other obesity-related medical conditions, modest and sustained weight loss improves glycemic control, blood pressure, and lipids and may reduce the need for medications to control these risk factors ( 6 – 8 , 32 ). Greater weight loss may produce even greater benefits ( 20 , 21 ). For a more detailed discussion of lifestyle management approaches and recommendations see Section 5 “Facilitating Behavior Change and Well-being to Improve Health Outcomes” ( https://doi.org/10.2337/dc21-S005 ). For a detailed discussion of nutrition interventions, please also refer to “Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report” ( 33 ).

Look AHEAD Trial

Although the Action for Health in Diabetes (Look AHEAD) trial did not show that the intensive lifestyle intervention reduced cardiovascular events in adults with type 2 diabetes and overweight or obesity ( 34 ), it did confirm the feasibility of achieving and maintaining long-term weight loss in patients with type 2 diabetes. In the intensive lifestyle intervention group, mean weight loss was 4.7% at 8 years ( 35 ). Approximately 50% of intensive lifestyle intervention participants lost and maintained ≥5% of their initial body weight, and 27% lost and maintained ≥10% of their initial body weight at 8 years ( 35 ). Participants assigned to the intensive lifestyle group required fewer glucose-, blood pressure–, and lipid-lowering medications than those randomly assigned to standard care. Secondary analyses of the Look AHEAD trial and other large cardiovascular outcome studies document additional benefits of weight loss in patients with type 2 diabetes, including improvements in mobility, physical and sexual function, and health-related quality of life ( 26 ). Moreover, several subgroups had improved cardiovascular outcomes, including those who achieved >10% weight loss ( 36 ) and those with moderately or poorly controlled diabetes (A1C >6.8%) at baseline ( 37 ).

Lifestyle Interventions

Significant weight loss can be attained with lifestyle programs that achieve a 500–750 kcal/day energy deficit, which in most cases is approximately 1,200–1,500 kcal/day for women and 1,500–1,800 kcal/day for men, adjusted for the individual's baseline body weight. Clinical benefits typically begin upon achieving 3–5% weight loss ( 19 , 38 ), and the benefits of weight loss are progressive; more intensive weight-loss goals (>5%, >7%, >15%, etc.) may be pursued if needed to achieve further health improvements and/or if the patient is more motivated and more intensive goals can be feasibly and safely attained.

Dietary interventions may differ by macronutrient goals and food choices as long as they create the necessary energy deficit to promote weight loss ( 19 , 39 – 41 ). Use of meal replacement plans prescribed by trained practitioners, with close patient monitoring, can be beneficial. Within the intensive lifestyle intervention group of the Look AHEAD trial, for example, use of a partial meal replacement plan was associated with improvements in diet quality and weight loss ( 38 ). The diet choice should be based on the patient's health status and preferences, including a determination of food availability and other cultural circumstances that could affect dietary patterns ( 42 ).

Intensive behavioral lifestyle interventions should include ≥16 sessions in 6 months and focus on dietary changes, physical activity, and behavioral strategies to achieve an ∼ 500 – 750 kcal/day energy deficit. Interventions should be provided by trained interventionists in either individual or group sessions ( 38 ). Assessing an individual's motivation level, life circumstances, and willingness to implement lifestyle changes to achieve weight loss should be considered along with medical status when weight-loss interventions are recommended and initiated ( 31 , 43 ).

Patients with type 2 diabetes and overweight or obesity who have lost weight should be offered long-term (≥1 year) comprehensive weight-loss maintenance programs that provide at least monthly contact with trained interventionists and focus on ongoing monitoring of body weight (weekly or more frequently) and/or other self-monitoring strategies such as tracking intake, steps, etc.; continued focus on dietary and behavioral changes; and participation in high levels of physical activity (200 – 300 min/week) ( 44 ). Some commercial and proprietary weight-loss programs have shown promising weight-loss results, though most lack evidence of effectiveness, many do not satisfy guideline recommendations, and some promote unscientific and possibly dangerous practices ( 45 , 46 ).

When provided by trained practitioners in medical settings with ongoing monitoring, short-term (generally up to 3 months) intensive dietary intervention may be prescribed for carefully selected patients, such as those requiring weight loss prior to surgery and persons needing greater weight loss and glycemic improvements. When integrated with behavioral support and counseling, structured very-low-calorie diets, typically 800–1,000 kcal/day utilizing high-protein foods and meal replacement products, may increase the pace and/or magnitude of initial weight loss and glycemic improvements compared with standard behavioral interventions ( 20 , 21 ). As weight regain is common, such interventions should include long-term, comprehensive weight-maintenance strategies and counseling to maintain weight loss and behavioral changes ( 47 , 48 ).

Health disparities adversely affect groups of people who have systematically experienced greater obstacles to health based on their race or ethnicity, socioeconomic status, gender, disability, or other factors. Overwhelming research shows that these disparities may significantly affect health outcomes, including increasing the risk for diabetes and diabetes-related complications. Health care providers should evaluate systemic, structural, and socioeconomic factors that may impact food choices, access to healthful foods, and dietary patterns; other behavioral patterns, such as neighborhood safety and availability of safe outdoor spaces for physical activity; environmental exposures; access to health care; social contexts; and, ultimately, diabetes risk and outcomes. For a detailed discussion of social determinants of health, please refer to “Social Determinants of Health: A Scientific Review” ( 49 ).

8.12 When choosing glucose-lowering medications for patients with type 2 diabetes and overweight or obesity, consider the medication's effect on weight. B

8.13 Whenever possible, minimize medications for comorbid conditions that are associated with weight gain. E

8.14 Weight-loss medications are effective as adjuncts to diet, physical activity, and behavioral counseling for selected patients with type 2 diabetes and BMI ≥27 kg/m 2 . Potential benefits and risks must be considered. A

8.15 If a patient’s response to weight-loss medication is effective (typically defined as >5% weight loss after 3 months’ use), further weight loss is likely with continued use. When early response is insufficient (typically <5% weight loss after 3 months’ use), or if there are significant safety or tolerability issues, consider discontinuation of the medication and evaluate alternative medications or treatment approaches. A

Glucose-Lowering Therapy

A meta-analysis of 227 randomized controlled trials of glucose-lowering treatments in type 2 diabetes found that A1C changes were not associated with baseline BMI, indicating that patients with obesity can benefit from the same types of treatments for diabetes as normal-weight patients ( 50 ). As numerous effective medications are available, when considering medication regimens health care providers should consider each medication’s effect on weight. Agents associated with varying degrees of weight loss include metformin, α-glucosidase inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and amylin mimetics. Dipeptidyl peptidase 4 inhibitors are weight neutral. In contrast, insulin secretagogues, thiazolidinediones, and insulin are often associated with weight gain (see Section 9 “Pharmacologic Approaches to Glycemic Treatment,” https://doi.org/10.2337/dc21-s009 ).

Concomitant Medications

Providers should carefully review the patient's concomitant medications and, whenever possible, minimize or provide alternatives for medications that promote weight gain. Examples of medications associated with weight gain include antipsychotics (e.g., clozapine, olanzapine, risperidone, etc.), some antidepressants (e.g., tricyclic antidepressants, some selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors), glucocorticoids, injectable progestins, some anticonvulsants (e.g., gabapentin, pregabalin), and possibly sedating antihistamines and anticholinergics ( 51 ).

Approved Weight-Loss Medications

The U.S. Food and Drug Administration (FDA) has approved medications for both short-term and long-term weight management as adjuncts to diet, exercise, and behavioral therapy. Nearly all FDA-approved medications for weight loss have been shown to improve glycemic control in patients with type 2 diabetes and delay progression to type 2 diabetes in patients at risk ( 52 ). Phentermine and other older adrenergic agents are indicated for short-term (≤12 weeks) treatment ( 53 ). Four weight-loss medications are FDA approved for long-term use (>12 weeks) in patients with BMI ≥27 kg/m 2 with one or more obesity-associated comorbid condition (e.g., type 2 diabetes, hypertension, and/or dyslipidemia) who are motivated to lose weight ( 52 ). Medications approved by the FDA for the treatment of obesity are summarized in Table 8.2 . The rationale for weight-loss medication use is to help patients adhere to dietary recommendations, in most cases by modulating appetite or satiety. Providers should be knowledgeable about the product label and should balance the potential benefits of successful weight loss against the potential risks of the medication for each patient. These medications are contraindicated in women who are pregnant or actively trying to conceive and not recommended for use in women who are nursing. Women of reproductive potential should receive counseling regarding the use of reliable methods of contraception.

Medications approved by the FDA for the treatment of obesity

All medications are contraindicated in women who are or may become pregnant. Women of reproductive potential must be counseled regarding the use of reliable methods of contraception. Select safety and side effect information is provided; for a comprehensive discussion of safety considerations, please refer to the prescribing information for each agent. b.i.d., twice daily; ER, extended release; OTC, over the counter; PBO, placebo; q.d., daily; Rx, prescription; t.i.d., three times daily.

Use lowest effective dose; maximum appropriate dose is 37.5 mg.

Duration of treatment was 28 weeks in a general obese adult population.

Agent has demonstrated cardiovascular safety in a dedicated cardiovascular outcome trial ( 127 ).

Enrolled participants had normal (79%) or impaired (21%) glucose tolerance.

Maximum dose, depending on response, is 15 mg/92 mg q.d.

Approximately 68% of enrolled participants had type 2 diabetes or impaired glucose tolerance.

Assessing Efficacy and Safety

Upon initiating weight-loss medication, assess efficacy and safety at least monthly for the first 3 months and at least quarterly thereafter. Modeling from published clinical trials consistently shows that early responders have improved long-term outcomes ( 54 – 56 ). Unless clinical circumstances (such as poor tolerability) or other considerations (such as financial expense or patient preference) suggest otherwise, those who achieve sufficient early weight loss upon starting a chronic weight-loss medication (typically defined as >5% weight loss after 3 months’ use) should continue the medication. When early use appears ineffective (typically <5% weight loss after 3 months’ use), it is unlikely that continued use will improve weight outcomes; as such, it should be recommended to discontinue the medication and consider other treatment options.

Several minimally invasive medical devices have been approved by the FDA for short-term weight loss ( 57 , 58 ). It remains to be seen how these are used for obesity treatment. Given the high cost, limited insurance coverage, and paucity of data in people with diabetes at this time, medical devices for weight loss are currently not considered to be the standard of care for obesity management in people with type 2 diabetes.

8.16 Metabolic surgery should be a recommended option to treat type 2 diabetes in screened surgical candidates with BMI ≥40 kg/m 2 (BMI ≥37.5 kg/m 2 in Asian Americans) and in adults with BMI 35.0–39.9 kg/m 2 (32.5–37.4 kg/m 2 in Asian Americans) who do not achieve durable weight loss and improvement in comorbidities (including hyperglycemia) with nonsurgical methods. A

8.17 Metabolic surgery may be considered as an option to treat type 2 diabetes in adults with BMI 30.0–34.9 kg/m 2 (27.5–32.4 kg/m 2 in Asian Americans) who do not achieve durable weight loss and improvement in comorbidities (including hyperglycemia) with nonsurgical methods. A

8.18 Metabolic surgery should be performed in high-volume centers with multidisciplinary teams knowledgeable about and experienced in the management of diabetes and gastrointestinal surgery. E

8.19 Long-term lifestyle support and routine monitoring of micronutrient and nutritional status must be provided to patients after surgery, according to guidelines for postoperative management of metabolic surgery by national and international professional societies. C

8.20 People being considered for metabolic surgery should be evaluated for comorbid psychological conditions and social and situational circumstances that have the potential to interfere with surgery outcomes. B

8.21 People who undergo metabolic surgery should routinely be evaluated to assess the need for ongoing mental health services to help with the adjustment to medical and psychosocial changes after surgery. C

Several gastrointestinal (GI) operations, including partial gastrectomies and bariatric procedures ( 44 ), promote dramatic and durable weight loss and improvement of type 2 diabetes in many patients. Given the magnitude and rapidity of the effect of GI surgery on hyperglycemia and experimental evidence that rearrangements of GI anatomy similar to those in some metabolic procedures directly affect glucose homeostasis ( 45 ), GI interventions have been suggested as treatments for type 2 diabetes, and in that context they are termed “metabolic surgery.”

A substantial body of evidence has now been accumulated, including data from numerous randomized controlled (nonblinded) clinical trials, demonstrating that metabolic surgery achieves superior glycemic control and reduction of cardiovascular risk factors in patients with type 2 diabetes and obesity compared with various lifestyle/medical interventions ( 17 ). Improvements in microvascular complications of diabetes, cardiovascular disease, and cancer have been observed only in nonrandomized observational studies ( 59 – 70 ). Cohort studies attempting to match surgical and nonsurgical subjects suggest that the procedure may reduce longer-term mortality ( 60 , 71 ).

While several surgical options are available, the overwhelming majority of procedures in the U.S. are vertical sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). Both procedures result in an anatomically smaller stomach pouch and often robust changes in enteroendocrine hormones. On the basis of this mounting evidence, several organizations and government agencies have recommended expanding the indications for metabolic surgery to include patients with type 2 diabetes who do not achieve durable weight loss and improvement in comorbidities (including hyperglycemia) with reasonable nonsurgical methods at BMIs as low as 30 kg/m 2 (27.5 kg/m 2 for Asian Americans) ( 72 – 79 ). Randomized controlled trials have documented diabetes remission during postoperative follow-up ranging from 1 to 5 years in 30–63% of patients with RYGB, which generally leads to greater degrees and lengths of remission compared with other bariatric surgeries ( 17 , 80 ). Available data suggest an erosion of diabetes remission over time ( 81 ): 35–50% or more of patients who initially achieve remission of diabetes eventually experience recurrence. However, the median disease-free period among such individuals following RYGB is 8.3 years ( 82 , 83 ). With or without diabetes relapse, the majority of patients who undergo surgery maintain substantial improvement of glycemic control from baseline for at least 5 years ( 84 , 85 ) to 15 years ( 60 , 61 , 83 , 86 – 88 ).

Exceedingly few presurgical predictors of success have been identified, but younger age, shorter duration of diabetes (e.g., <8 years) ( 89 ), nonuse of insulin, maintenance of weight loss, and better glycemic control are consistently associated with higher rates of diabetes remission and/or lower risk of weight regain ( 60 , 87 , 89 , 90 ). Greater baseline visceral fat area may also help to predict better postoperative outcomes, especially among Asian American patients with type 2 diabetes, who typically have more visceral fat compared with Caucasians with diabetes of the same BMI ( 91 ). Beyond improving glycemia, metabolic surgery has been shown to confer additional health benefits in randomized controlled trials, including substantial reductions in cardiovascular disease risk factors ( 17 ), reductions in incidence of microvascular disease ( 92 ), and enhancements in quality of life ( 84 , 89 , 93 ).

Although metabolic surgery has been shown to improve the metabolic profiles of patients with type 1 diabetes and morbid obesity, establishing the role of metabolic surgery in such patients will require larger and longer studies ( 94 ).

Metabolic surgery is more expensive than nonsurgical management strategies, but retrospective analyses and modeling studies suggest that metabolic surgery may be cost-effective or even cost-saving for patients with type 2 diabetes. However, results are largely dependent on assumptions about the long-term effectiveness and safety of the procedures ( 95 , 96 ).

Adverse Effects

The safety of metabolic surgery has improved significantly over the past several decades, with continued refinement of minimally invasive approaches (laparoscopic surgery), enhanced training and credentialing, and involvement of multidisciplinary teams. Mortality rates with metabolic operations are typically 0.1–0.5%, similar to cholecystectomy or hysterectomy ( 97 – 101 ). Morbidity has also dramatically declined with laparoscopic approaches. Major complications and need for operative reintervention occur in 2–6% of those undergoing bariatric surgery, with other minor complications in up to 15% ( 97 – 106 ). These rates compare favorably with those for other commonly performed elective operations ( 101 ). Empirical data suggest that proficiency of the operating surgeon is an important factor for determining mortality, complications, reoperations, and readmissions ( 107 ). Accordingly, metabolic surgery should be performed in high-volume centers with multidisciplinary teams knowledgeable about and experienced in the management of diabetes and GI surgery.

Longer-term concerns include dumping syndrome (nausea, colic, and diarrhea), vitamin and mineral deficiencies, anemia, osteoporosis, and severe hypoglycemia ( 108 ). Long-term nutritional and micronutrient deficiencies and related complications occur with variable frequency depending on the type of procedure and require lifelong vitamin/nutritional supplementation; thus, long-term lifestyle support and routine monitoring of micronutrient and nutritional status should be provided to patients after surgery ( 109 , 110 ). Postprandial hypoglycemia is most likely to occur with RYGB ( 110 , 111 ). The exact prevalence of symptomatic hypoglycemia is unknown. In one study, it affected 11% of 450 patients who had undergone RYGB or vertical sleeve gastrectomy ( 108 ). Patients who undergo metabolic surgery may be at increased risk for substance use, including drug and alcohol use and cigarette smoking. Additional potential risks of metabolic surgery that have been described include worsening or new-onset depression and/or anxiety, need for additional GI surgery, and suicidal ideation ( 112 – 115 ).

People with diabetes presenting for metabolic surgery also have increased rates of depression and other major psychiatric disorders ( 116 ). Candidates for metabolic surgery with histories of alcohol, tobacco, or substance abuse or significant depression, suicidal ideation, or other mental health conditions should therefore first be assessed by a mental health professional with expertise in obesity management prior to consideration for surgery ( 117 ). Surgery should be postponed in patients with alcohol or substance abuse disorders, significant depression, suicidal ideation, or other mental health conditions until these conditions have been fully addressed. Individuals with preoperative psychopathology should be assessed regularly following metabolic surgery to optimize mental health management and to ensure that psychiatric symptoms do not interfere with weight loss and lifestyle changes.

Suggested citation: American Diabetes Association. 8. Obesity management for the treatment of type 2 diabetes: Standards of Medical Care in Diabetes—2021 . Diabetes Care 2021;44(Suppl. 1):S100–S110

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• Published: 18 April 2024

An algorithm for the use of anti-obesity medications

• Fereshteh Dehghani   ORCID: orcid.org/0000-0002-5997-098X 1 ,
• Mitra Ali Ahmadi 1   na1 ,
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Reduced energy diet and increased physical activity form the cornerstone of medical management of obesity. However, long-term adherence to a restricted diet is highly challenging [ 1 ]. Anti-obesity medications (AOM) help to resist food cravings, reduce hunger, or increase satiety, thereby empowering individuals to adhere to a restricted diet and promote greater weight loss [ 2 ]. Therefore, AOM are needed, not as a substitute, but as a supplement to lifestyle modification efforts for weight management. The concept of pharmacological support for obesity treatment is similar to the use of medications for other chronic diseases with a behavioral component, such as diabetes or hypertension. Fortunately, several drug options are now available to treat hypertension or diabetes. And, in case of a suboptimal response of an individual to a drug, a health care provider (HCP) may choose a different drug or a different set of drugs. Similarly, if an individual is a poor responder to a particular AOM, that drug may still help another individual, and a different AOM may be more effective for the person who did not respond initially [ 3 ].

Often, the drug selection for treatment is based on many criteria, including accompanying comorbidities, prior response to medications, potential adverse events, and drug costs. For example, for diabetes treatment, secretagogues, mimetic, or sensitizers of insulin may be selected depending on the individual’s pathophysiology and circumstances. Similarly, AOM are comprised of medications with a range of target pathways, adverse event profiles, routes of administration, costs, and weight loss response [ 2 ].

However, AOM face additional challenges in recognition of their need for obesity management. While diabetes is widely recognized as a disease that needs aggressive medical attention, obesity may not be viewed by the patients or some HCPs as a serious disease that needs lifelong management, including pharmacotherapy. Furthermore, due to the refractory nature of obesity, resource intense treatment, and limited health insurance coverage, the window of opportunity to treat obesity is limited. Individuals with obesity who are less successful in an initial weight loss attempt are likely to abandon treatment and are less likely to initiate a new weight management attempt [ 4 ]. In addition, there are a limited number of Food and Drug Administration (FDA)-approved AOMs for long-term care. Therefore, a careful matching of AOM to an individual’s need is needed to maximize the chances of weight loss success. Hence, we propose an algorithm based on the indications of various FDA-approved AOM. First, a very brief description of AOM is merited.

Drug description

Glucagon-like peptide-1 (glp-1) receptor agonist.

This class of drugs, like Liraglutide and Semaglutide, mimics the action of glucagon-like peptide-1 and help regulate appetite. These drugs are intended for use by adults and children (≥12 years) with obesity or by adults with overweight (body mass index (BMI) ≥ 27) in the presence of weight-related comorbidities (Source: www.saxenda.com ; www.wegovy.com ).

Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist

This medication (Tirzepatide), when combined with calorie-deficit diet and exercise, is helpful for managing weight in adult with obesity or overweight individuals who have weight-related comorbidities (Source: www.zepbound.lilly.com ).

Phentermine/Topiramate

Phentermine and Topiramate work together to control hunger and reduce cravings. This medication should be used in combination with a reduced-calorie diet and increased physical activity by patients aged 12 years and older with obesity or by adults with overweight (BMI ≥ 27) having weight-related comorbidities (Source: www.qsymia.com ).

Hydrogel (Plenity)

This hydrogel capsule works by expanding in the stomach, creating a feeling of fullness and usually taken before meals with water. Hydrogel is recommended to help with weight management in adults with overweight or obesity (BMI 25–40) in combination with diet and exercise (Source: www.myplenity.com ).

Naltrexone/Bupropion

Naltrexone and Bupropion work together to reduce hunger and control cravings and recommended in combination with lifestyle modifications in adults with obesity or overweight (BMI ≥ 27) and have weight-related medical conditions (Source: www.contrave.com ).

Setmelanotide

This medication is to be used only in adults and children 6 years of age and older who have obesity due to deficiency of POMC, PCSK1, or the leptin receptor (Source: www.imcivree.com ).

Orlistat inhibits fat absorption in the intestine and is indicated to aid weight loss with a reduced-calorie, low-fat diet. This drug is for adults only with obesity or overweight (BMI ≥ 27) who have risk factors like hypertension, diabetes, dyslipidemia. The over-the-counter version of orlistat (60 mg), can be taken by overweight adults with a BMI ≥ 25 (Source: www.xenical.com , www.myalli.com ).

Describing the algorithm

A major consideration for AOM prescription is BMI and the presence of weight-related comorbid conditions. The next consideration is age, as some AOM are approved for use only in adults. Fortunately, there are some AOM that could be used in children up to 12 years of age, and at least one medication for use starting at 6 years of age. The next set of considerations are based on creative matching of drug indications with corresponding need of an individual. For example, considering their dual effect on glycemic control improvement and weight loss, GLP1 receptor agonists may be the first consideration for individuals with hyperglycemia accompanying obesity. While they may have overlapping indications, AOM could also be differentiated based on their key potential to address hunger, satiety, or food cravings. Detailed questioning of patients can reveal if the main challenge is feeling unusually hungry or having difficulty feeling satiated in good time. The combination of topiramate with long-acting phentermine may be considered to address hunger, while the GLP-1 receptor agonists could be used if delayed satiety is the main issue. Another anti-obesity device expected to work by inducing satiety is hydrogel, which when consumed as a pill absorbs water and swells in the stomach, thereby reducing stomach volume and promoting fullness. The combination of naltrexone and bupropion may be beneficial if the patient has “food cravings” as a primary concern influencing food intake. Severe hunger and childhood onset of extreme obesity may suggest obesity due to specific genetic mutations, for which setmelanotide may be indicated. This medication is available for children as young as 6 years, who have the specific gene mutations. A condition to differentiate from excessive hunger is binge eating disorder. Only a subset of individuals with obesity has the disorder, characterized by episodes of consumption of enormous amounts of food and a feeling of lack of control. The phentermine/topiramate combination, has also been reported to help in addressing the binge eating disorder. If eating high fat food such as fried food poses a barrier to achieving substantial negative energy balance, orlistat may be the right AOM to reduce the digestion of fat. An inquiry into sleep hygiene and quality may lead to sleep studies and detection of obstructive sleep apnea, a condition commonly associated with obesity. The topiramate/phentermine combination is reported to produce weight loss and simultaneous improvements in obstructive sleep apnea and its associated symptoms [ 5 ].

This algorithm focuses on currently available FDA approved AOM for long-term use (Fig. 1 ). As AOM, their fundamental indication is weight loss in individuals with obesity and may be used regardless of the suggested algorithm. Effective weight loss itself may alleviate many obesity-associated comorbidities without the use of an AOM with specific indication. Furthermore, clinical decisions for selecting particular AOM for an individual may be guided by medical considerations such as contra-indications or cautions for each AOM as well as non-medical considerations including cost, personal preference, and availability, which are not covered in this algorithm. However, this algorithm presents one approach to address additional needs of an individual with obesity to personalize the use of AOM, to maximize the benefits.

Arrow styles indicate the BMI and age groups approved for receiving obesity medications listed below.

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These authors contributed equally: Mitra Ali Ahmadi, Marleigh Hefner, Gaurav Kudchadkar, Wasiuddin Najam, Masoud Nateqi, Md Abu Bakkar Siddik.

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Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA

Fereshteh Dehghani, Mitra Ali Ahmadi, Marleigh Hefner, Gaurav Kudchadkar, Masoud Nateqi, Md Abu Bakkar Siddik, Holli Booe & Nikhil V. Dhurandhar

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA

Wasiuddin Najam

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NVD and HB contributed to conceptualization. FD, MAA, MH, GK, WN, MN, MABS, HB, and ND performed the review of literature and contributed to writing. All authors contributed to the manuscript revision, read, and approved the submitted version.

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Dehghani, F., Ali Ahmadi, M., Hefner, M. et al. An algorithm for the use of anti-obesity medications. Nutr. Diabetes 14 , 20 (2024). https://doi.org/10.1038/s41387-024-00278-2

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Obesity differs from diabetes mellitus in antibody and t cell responses post covid-19 recovery.

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Mohammad Ali, Stephanie Longet, Isabel Neale, Patpong Rongkard, Forhad Uddin Hassan Chowdhury, Jennifer Hill, Anthony Brown, Stephen Laidlaw, Tom Tipton, Ashraful Hoque, Nazia Hassan, Carl-Philipp Hackstein, Sandra Adele, Hossain Delowar Akther, Priyanka Abraham, Shrebash Paul, Md Matiur Rahman, Md Masum Alam, Shamima Parvin, Forhadul Hoque Mollah, Md Mozammel Hoque, Shona C Moore, Subrata K Biswas, Lance Turtle, Thushan I de Silva, Ane Ogbe, John Frater, Eleanor Barnes, Adriana Tomic, Miles W Carroll, Paul Klenerman, Barbara Kronsteiner, Fazle Rabbi Chowdhury, Susanna J Dunachie, Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery, Clinical and Experimental Immunology , 2024;, uxae030, https://doi.org/10.1093/cei/uxae030

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Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with obesity and DM in Bangladesh. In this cross-sectional study, SARS-CoV-2-specific antibody and T cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, obesity was associated with decreased neutralising antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8+ T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T cell responses after adjustment for obesity and other confounders. Obesity is associated with lower neutralising antibody levels and higher T cell responses to SARS-CoV-2 post COVID-19 recovery, while antibody or T cell responses remain unaltered in DM.

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Diabetes is a complex disease that affects millions of people worldwide. Diabetes is a metabolic disease, in which increased blood glucose levels ultimately lead to heart disease, stroke, kidney failure, foot ulcers, and damage to the eyes. Current prevalence rates of diabetes are extremely high in countries throughout the world. Multiple forms of diabetes have been identified, including type 1, type 2, type 3, neonatal and gestational. The purpose of this article is to discuss recent developments in diabetes research, including prevalence, morbidity and mortality rates, and lifestyle factors that are associated with diabetes onset and progression. This article also discusses how lifestyle factors delay and or prevent diabetes.

Diabetes is a chronic disease that affects millions of people worldwide. Diabetes is mostly polygenic condition, accounts for about 95% of total diabetes cases and it is mostly late- onset. Genetic mutations in single gene cause diabetes, referred monogenic. Monogenic forms of diabetes accounts for about 1-5% of all cases diabetes and monogenic diabetes occur in young people [ 1 ]. Genetic mutations in monogenic form of diabetes reduce the production of hormone insulin in the beta cells of pancreas, which is responsible for the maintenance of blood glucose level. Diabetes is a collection of multiple metabolic diseases, in which high levels of blood glucose are present over an extended period of time. Most persons with diabetes remain undiagnosed early in the disease process [ 2 ]. In most cases, blood glucose levels in persons with diabetes increase with age, leading to heart disease, stroke, chronic kidney failure, foot ulcers, and damage to the eyes. Such high glucose levels are associated with frequent urination and increased thirst and hunger.

The purpose of this mini-review is to explain recent research findings in investigations of diabetes, including:

a. Prevalence,

b. Morbidity and mortality rates,

c. Types of diabetes,

d. Factors that affect diabetes and

e. Current research findings about diabetes therapeutics.

Prevalence of diabetes

The worldwide prevalence of diabetes was 2.8% in 2000, and it is expected to increase to 4.4% by 2030. The total number of persons with diabetes worldwide is estimated to increase from 171 million in 2000 to 366 million in 2030 [ 3 ]. The most important demographic change regulating to diabetes prevalence across the world is that it is increasing in people older than 65 years [ 3 ]. According to the Center for Disease Control and Prevention, in the United States the number of persons with diabetes older than 65 years of age rose nearly 300% between 1980 and 2014, from 5.5 million in 1980 to 22 million in 2014. The percentage of Americans age 65years of age or older remains high at 25.9%, with 1.4 million Americans diagnosed with diabetes each year [ 4 ].

Morbidity and mortality rates of persons with diabetes

Acute complications from diabetes include diabetic ketoacidosis, a life-threatening condition that develops especially in persons with type1 diabetes, when cells in the body are unable to get the glucose they need for energy due to insulin insufficiency. When glucose cannot get into the cells, it stays in the blood. The kidneys filter some of the sugar from the blood and remove it through urine. But when cells cannot receive sugar for energy, the body begins breaking down fat and muscle for energy. When this occurs, fatty acids are produced and enter the bloodstream, causing a life-threatening chemical imbalance called diabetic ketoacidosis.

Another acute complication from diabetes is nonketotic hyperosmolar coma, which is when blood sugar levels rise, and the body tries to get rid of the excess sugar by passing it into the urine, initially resulting in increased urination. However, at later stages, urination decreases and thirst increases. Without sufficient liquids, dehydration can result, leading to seizures, a coma, and eventually death. This process may take days or even weeks to develop. Persons with type 1 and type 2 diabetes may succumb to this complication.

Current morbidity and mortality rates of persons with diabetes are very high in the United States (Statistics about diabetes, American Diabetes Association. According to the American Diabetes Association, from 2009 to 2012, of the adults aged 18 years or older who were with diagnosed diabetes, 71% had increased blood pressure and 65% had LDL cholesterol levels greater than normal (Statistics about diabetes, American Diabetes Association. Based on statistics from 2003 to 2006, cardiovascular disease death rates were about 1.7 times higher among adults with diagnosed diabetes who were aged 18 years or older compared to adults who did not receive a diabetes diagnosis, after adjusting for age differences in these population groups. In 2010, hospitalization rates due to heart attack were 1.8 times higher among adults diagnosed with diabetes who were aged 20 years or older [ 4 , 5 ]. Also in 2010, after adjusting for age differences, hospitalization rates for victims of stroke were 1.5 times higher among adults diagnosed with diabetes [ 5 ].

In 2005 to 2008, of the adults with diabetes aged 40 years or older, 4.2 million (28.5%) had diabetic retinopathy, that is, damage to the small blood vessels in the retina, which can ultimately result in loss of vision [ 4 , 5 ]. In 2011, diabetes was listed as the primary cause of kidney failure in 44% of all new cases of kidney failure.

And in this same year, a total of 228,924 people of all ages who were diagnosed with kidney failure were living on chronic dialysis except for those who had a kidney transplant [ 4 , 5 ]. A recent 2017 study reported that health problems associated with diabetes had been significantly underreported in the United States, and that Americans with diabetes have about a 90% higher death rate than those without diabetes [ 6 ]. These rates of illnesses, morbidity, and mortality figures underscore diabetes as a major and increasing health concern.

Cost of diabetes

In 2012, the costs of treating illnesses associated with diabetes, such as blindness, heart attack, and stroke, rose to $245 billion in the United States, with direct medical costs of about $176 billion. After adjusting for age and sex differences in persons diagnosed with diabetes, their average medical expenditures were found to be 2.3 times higher than for persons without diabetes [ 4 , 5 ].

Types of diabetes

The levels of glucose in the blood determine the severity of diabetes, but the age of diabetes onset usually determines its type. Multiple forms of diabetes have been identified, including type 1, type 2, type 3, neonatal and, gestational [ 2 , 7 , 8 ].

Type 1 diabetes: Type 1 diabetes is early-onset, usually when the patient is 30 years of age or younger. Five percent of the total number of diabetic patients has type 1. Type 1 diabetes occurs after first 6 months of life. Early-onset, type 1is typically associated with inherited gene mutations [ 2 ]. Type 1 diabetes is also called an insulin-dependent diabetes because persons with type 1 diabetes need to manage their blood glucose levels through insulin shots.

Type 2 diabetes: Type diabetes is a late-onset disease, in that its symptoms first appear in persons older than 30 years of age. Type 2 diabetes covers over 90% of the total diabetic population. Type 2 diabetes encompasses persons with higher- than-normal blood sugar levels, which may lead to increased insulin resistance and insulin deficiency [ 2 , 10 ]. Type 2 diabetes is associated with some non-modifiable and some modifiable risk factors.

Type 3 diabetes: Type 3 diabetes has been identified as a possible form of Alzheimer's disease [ 2 , 8 ]. Persons with type 3 diabetes exhibit cognitive impairment and oxidative stress that affect glucose metabolism symptoms that also characterize persons with AD, in terms of insulin resistance, and mitochondrial dysfunction. Several recent studies have also shown underlying, mechanistic links across metabolic changes and carbohydrates, lipids, proteins, and brain dysfunction in persons with AD and in persons with type 3 diabetes [ 8 ].

Neonatal diabetes: Neonatal diabetes occurs in the first six months of life and it is monogenic. It is a condition occurs one in 100,000 to 500,000 live births. Infants with neonatal diabetes do not produce sufficient insulin and this condition often confused with type 1 diabetes.

Gestational diabetes: Gestational diabetes is the onset of diabetes in mothers during pregnancy, typically accompanying carbohydrate intolerance. Gestational diabetes is usually diagnosed at later stages of pregnancy.

The following conditions are associated with gestational diabetes in pregnant mothers:

a. Age 25 or older,

b. Over weight mother, particularly body mass index is 30 or higher,

c. Mothers have polycystic ovarian syndrome,

d. Have a medical condition that makes diabetes more likely, such as glucose intolerance,

e. Mothers, who take medications like glucocorticoids for asthma or an autoimmune disease,

f. Mothers who take beta-blockers for high blood pressure, or antipsychotic drugs and

g. Mothers who African American, Native American, Asian American, Hispanic, or Pacific Islander [ 2 , 10 ].

Mechanistic action in diabetes: Hypoglycemic hormone, insulin is produced by the pancreas. In turn, insulin regulates glucose metabolism which also in turn regulates plasma glucose. Genetic abnormalities of insulin gene lead to insufficient and/ or defective production of insulin, typically leading to type 1 diabetes [ 2 ]. In type 2 diabetes, the body is unable to regulate sugar levels in the blood. Several factors are involved in sugar level regulation in type 2 diabetes, including genetic and environmental interactions and increased calorie intake (high fat diet) and lack of exercise. All of these factors induce insulin- related abnormalities, ultimately leading to events that cause late-onset type 2 diabetes. Overall, the elevated level of blood glucose is due to the failure of beta cells in the pancreas to produce insulin or to regulate insulin resistance.

Modifiable and non-modifiable factors associated with diabetes: There are many factors associated with the onset of diabetes, some of which are modifiable and some not modifiable.

b.Non-modifiable factors: Sex, age, ethnicity, and changes in genomes are major non-modifiable factors. People over 65 are likely to develop pre-diabetes, and most with type 1 and type 2 diabetes are unaware of their pre-diabetic conditions. People have increased risk of developing pre-diabetes after age 40 years of age [ 2 ]. Individuals with inherited DNA changes in the genome are susceptible to diabetes.

I.Ethnicity: Ethnicity plays a key role in development of pre-diabetes. Some ethnic groups carry a higher risk of developing diabetes. These ethnics groups are Africans, Alaskan Natives, American Indians, Asians, Latinos, and individuals of Pacific Islander descent.

II. Genetics: Changes in the genome contribute significantly to both early-onset type 1 and late-onset type 2 diabetes. Individuals with polymorphisms in individual genes in the genome are likely to be obese and to develop pre-diabetes and diabetes [ 7 ]. Polymorphisms in the genes HLA-DQA1, HLA- DQB1, and HLA-DRB1 in persons with diabetes have been found to correlate with the development of type 1diabetes [ 7 ]. Genetic polymorphisms in these genes alter proteins play critical roles in the immune system of type 1 diabetes. It is likely that interactions between genome changes with environmental conditions and/ or diet promote obesity, pre-diabetes, and diabetes in human populations. In addition, epigenetic factors, including diet and lifestyle are other major contributors to the development of obesity, pre-diabetes, and diabetes.

III.Exercise: Exercise plays an important role in the maintenance of body weight and blood sugar levels and in reducing pre-diabetes symptoms. Health benefits associated with physical activity are rapidly being identified. For example, exercise improves blood circulation, reduces the risk of heart disease, reduces the risk of stroke, improves self-esteem, and improves whole-body blood glucose levels [ 11 ]. Some exercises may also improve changes in skeletal muscle since skeletal muscle is responsible for the disposal of glucose from the blood. In addition, white adipose tissue shows beneficial effects with physical activity and exercise [ 11 ].

IV.Diet: Diet plays a significant role in the maintenance of blood sugar levels in in persons who are obese or who have pre-diabetes and diabetes symptoms. Mounting evidence suggests that nutritional therapy is useful for improving glycemic control and metabolism. Recent research into diabetes also suggests the importance of using evidence-based, rather than anecdotal-based, nutritional therapy that is based on a patient's level of insulin [ 12 - 14 ]. Nutritional education in diabetes selfmanagement programs is a critical component of a therapeutic plan for persons with diabetes.

V. Education and awareness: An awareness of and education about obesity, pre-diabetes conditions, and diabetes are important for persons with diabetes to consider changing their lifestyle. Educational material is available from clinics and local hospitals, and even from online sources. But currently, it is the responsibility of persons with diabetes to seek out these educational materials. Self-management classes about diabetes and lifestyle choices may be useful in providing persons with information to help them maintain the best quality of life possible, given their diabetes and in providing pre-diabetic persons information to help them avoid becoming diabetic [ 12 , 15 ]. The main objective of these self-management classes is teaching persons, self-sufficiency in using problem-solving skills to lead a healthier life. Overall, such self-management education has been an effective tool in reducing diabetes in persons currently at risk or in persons already diagnosed with the disease.

Research is being actively pursued to better understand molecular mechanisms underlying both type 1 and type 2 diabetes, using cell, rodent, nonhuman primate and human models [ 16 , 17 ]. Increasing evidence suggests that diabetes is a polygenic condition, in which DNA changes in multiple genes are involved in the development of diabetes. The regulation of genes has been found to change in persons with diabetes, and this dysregulation in turn affects the synthesis of proteins, a problem known to occur in persons with type 1 and type 2 diabetes.

In addition, elevated inflammatory responses, oxidative stress, and mitochondrial dysfunction are cellular events that have been extensively reported in obese persons and persons with type 1 and type 2 diabetes [ 18 ]. In these populations, defective regulation of insulin has been found to induce inflammation, oxidative stress, and mitochondrial dysfunction in tissues typically affected by diabetes, including tissues of the pancreas, liver, and brain, and skeletal muscles.

A naturally occurring mouse model for diabetes, the TallyHo mouse model, shows diabetic characteristics similar to those of humans with diabetes [ 19 ]. Genetic studies of TallyHo mice revealed that multiple DNA changes in multiple genes result in diabetic features found in humans with diabetes [ 19 - 21 ], including increased body weight, increased blood sugar levels, abnormal insulin regulation, and increased inflammation in the pancreas, liver, brain, and skeletal muscles. These features were found to increase with age in the TallyHo mice, just as they were found to increase with age in humans with diabetes [ 21 ]. It is possible that the types of polygenic changes found in the TallyHo mice also exist in humans with diabetes. Research is needed to better understand the molecular relationships between genome changes and diabetic characteristics in humans who have been so diagnosed.

Most recently, several researchers have newly proposed that AD is a type 3 diabetes, based on molecular similarities in obese persons with diabetes who exhibit insulin resistance and who also have AD [ 8 ]. These studies revealed that insulin is involved in the activation of the glycogen synthase kinase 3p, an enzyme that, in excess, results in the phosphorylation of tau. Phosphorylated tau is involved in the formation of neurofibrillary tangles, a hallmark of AD. Interestingly, insulin also plays a crucial role in the formation and increase of amyloid beta (AE), also a hallmark of brains from persons with AD.

Researchers in basic science, pharmaceutical companies, and clinicians worldwide are intensely working on identifying therapeutic targets that are capable of reducing abnormalities associated with diabetes, including the reduction of insulin resistance and insulin deficiency. However, no therapeutic targets have been identified. However, recent research into treatments for diabetes has resulted in several FDA-approved molecules that target diabetes. These FDA-approved products include Metformin, Januvia, and drugs with alpha-glucosidase inhibitors, such as Orlistat [ 2 ]. Since diabetes is a polygenic condition, researchers are attempting to develop genome- based treatments, based on the particular genetic composition of individual with diabetes rather than treatments designed for most persons with diabetes, regardless of their genetic makeup. Clinicians are also researching changes in lifestyle activities that could help maintain blood pressure and healthy blood sugar levels in persons with diabetes, with such lifestyle changes including increased daily exercise and a well-balanced diet that has no sugars, reduced fats, and fresh fruits and vegetables.

Since most people are undiagnosed early on in the diabetes disease process, increased education about symptoms of diabetes may lead persons to seek out health care providers early, rather than late, in the diabetes disease process and to learn how changes in their lifestyle activities can be reduce their symptoms of diabetes.

Work presented in this article is supported by NIH grants- AG042178 and AG047812 and the Garrison Family Foundation.

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From Fundamentals to the Clinic: Advancing Obesity Research in Endocrinology

Zeynep madak-erdogan.

Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

Stephen R Hammes

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA

M Furkan Burak

Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA

As the global obesity epidemic grows, it exerts profound effects on health, economies, and societies. The rising obesity rate is not only a health crisis but also a multifaceted challenge that intersects with economic burden and social disparities. Obesity is fundamentally linked to endocrine disorders, affecting hormones and metabolic processes critical to human health. Obesity significantly increases the risk for various chronic diseases—including infertility, type 2 diabetes, cardiovascular and pulmonary diseases, hypertension, and certain cancers—by disrupting metabolic and hormonal balance, promoting inflammation, and altering the body's normal functions. Addressing all aspects of obesity, which necessitates a broad approach in research and treatment, is crucial to prevent these associated health conditions and improve overall health outcomes.

The current landscape of obesity research is dynamic and rapidly evolving, reflecting the complex nature of obesity and the urgent need for effective therapies. There have recently been substantial advancements in understanding the biological pathways that regulate appetite, energy balance, and metabolism. This has helped develop new therapeutic strategies targeting different aspects of obesity, from appetite suppression to energy expenditure, from fat absorption to muscle mass preservation. Additionally, integrating digital health tools and personalized medicine approaches is becoming increasingly important in obesity management. These technologies can offer tailored dietary, exercise, and behavioral interventions, enhancing the effectiveness of pharmacological treatments and addressing the multifaceted nature of obesity.

Acknowledging and sharing scientific data on obesity's complexity is an important step toward innovative solutions to address the epidemic's roots and far-reaching consequences. Remarkable recent growth in obesity research is evidenced by the increasing number of articles published on obesity and metabolic disorders, with citations doubling over the past 5 years. This surge showcases the field's dynamism and its critical integration within the broader scope of endocrine studies. Interdisciplinary research can enhance understanding of obesity's role in endocrine diseases and promote the development of innovative treatments.

Researching and understanding all of these aspects of obesity align with JES's mission to advance medical science and improve patient care. Recognizing the growth in obesity research, we recently compiled a special collection of obesity-related articles published in JES ( https://academic.oup.com/jes/pages/obesity ). As a journal that publishes along the entire spectrum of research, from pure basic science to clinical to outcomes studies, we feel that JES is the ideal home for articles published on obesity. With the addition of our new associate editor, Dr Furkan Burak, on this topic and by encouraging submissions across a wide spectrum of obesity-related topics, our goal is to cultivate a rich and diverse discourse that reflects the complexity of the condition and fosters research excellence in the endocrinology of obesity. This approach ensures that we share high-quality research representing all facets of obesity, from molecular mechanisms to societal effects, enriching the field with varied perspectives and innovative solutions.

Despite scientific advances in obesity research, challenges remain in developing safe and effective obesity therapies. Thus, we issue a strong call to action for the scientific and medical communities to pursue the boundaries of obesity research and treatment relentlessly. The heterogeneity of obesity, with its various contributing factors, including genetics, lifestyle, and environmental influences, requires broad approaches. Moreover, the long-term safety and efficacy of emerging therapies must be established through rigorous clinical trials. Despite the recent emergence of novel, effective treatments, worldwide access to these treatments remains poor. Given the number of individuals with obesity and the current economic landscape of the obesity market, there is a race to bring untouched, previously nontargeted mechanism-of-action, genome-wide association study targets to clinic. We encourage the scientific community to maintain high standards of evidence, generate reproducible, robust data, and collaborate and share their resources such that we can effectively advance the obesity field worldwide. As research progresses, it is critical to ensure that these advances are accessible to the diverse populations affected by obesity, addressing not only physical but also psychological and societal dimensions of the disease. JES pledges its commitment to remain at the vanguard of disseminating groundbreaking research and fostering the development of effective solutions for obesity while increasing its accessibility. Through collective efforts and a shared vision, we can achieve significant strides in overcoming obesity and enhancing the well-being of individuals worldwide.

Disclosures

Z.M.E. is editor-in-chief, S.R.H. is deputy editor, and M.F.B. is an associate editor of Journal of the Endocrine Society .

Contributor Information

Zeynep Madak-Erdogan, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Stephen R Hammes, Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.

M Furkan Burak, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.