What medications are available for weight loss in diabetic patients?

From the Guidelines

For diabetic patients seeking weight loss, the most effective medication options are GLP-1 receptor agonists, such as semaglutide (Wegovy, Ozempic) and tirzepatide (Mounjaro, Zepbound), which offer significant weight loss of 15-20% while improving blood glucose control. These medications are typically started at low doses and gradually increased to minimize gastrointestinal side effects, such as nausea, vomiting, and diarrhea, which typically improve over time as the body adjusts to the medication 1.

Mechanism of Action

The GLP-1 receptor agonists work through various mechanisms, including appetite suppression, delayed gastric emptying, and increased satiety. Other options include liraglutide (Saxenda), which provides more modest weight loss of 5-10%, and orlistat (Xenical), which blocks fat absorption but has limited effectiveness 1. Metformin, while primarily for diabetes management, may produce modest weight loss of 2-3kg.

Lifestyle Modifications

These medications should be used alongside lifestyle modifications, including:

• Calorie restriction
• Increased physical activity
• High-intensity interventions (≥16 sessions in 6 months) focusing on dietary changes, physical activity, and behavioral strategies to achieve a 500–750 kcal/day energy deficit 1
• Ongoing monitoring of body weight (weekly or more frequently) and other self-monitoring strategies, including high levels of physical activity (200–300 min/week)

Recommendations

The American Diabetes Association recommends prioritizing medications with beneficial effects on weight, such as GLP-1 receptor agonists, for patients with type 2 diabetes and overweight or obesity 1. Weight management pharmacotherapy should be considered for people with diabetes and overweight or obesity, along with lifestyle changes, and potential benefits and risks must be considered 1.

Key Points

• GLP-1 receptor agonists are the most effective medication options for weight loss in diabetic patients
• Lifestyle modifications, including calorie restriction and increased physical activity, are essential for optimal results
• Medications should be used alongside lifestyle modifications to achieve and maintain significant weight loss
• Common side effects include nausea, vomiting, and diarrhea, which typically improve over time as the body adjusts to the medication 1

From the FDA Drug Label

The mean changes from baseline to week 56 were -4.8 kg and -2.0 kg in the OZEMPIC 1 mg and exenatide ER arms, respectively. The difference from exenatide ER (95% CI) for OZEMPIC 1 mg was -2.9 kg (-3.6, -2. 1). The mean changes from baseline to week 30 were -3.2 kg, -4.7 kg and 0.9 kg in the OZEMPIC 0.5 mg, OZEMPIC 1 mg, and insulin glargine arms, respectively. The difference from insulin glargine (95% CI) for OZEMPIC 0.5 mg was -4.1 kg (-4.9, -3.3) and for OZEMPIC 1 mg was -5.6 kg (-6.4, -4. 8). The mean changes from baseline to week 30 were -1.2 kg, -3.5 kg, and ‑6.0 kg in the placebo, OZEMPIC 0.5 mg, and OZEMPIC 1 mg arms, respectively. The difference from placebo (95% CI) for OZEMPIC 0.5 mg was -2.2 kg (-3.4, -1.1), and for OZEMPIC 1 mg was -4.7 kg (-5.8, -3.6).

Weight Loss Medications for Diabetics:

• Semaglutide (OZEMPIC) is a medication that has been shown to result in significant weight loss in diabetic patients.
• The medication can be used in combination with other therapies such as metformin, sulfonylurea, or basal insulin.
• Studies have demonstrated that semaglutide can lead to a mean weight loss of -4.8 kg to -6.0 kg over a period of 30-56 weeks, depending on the dose and combination therapy used.
• The difference in weight loss compared to placebo or other medications such as exenatide or insulin glargine was statistically significant, ranging from -2.2 kg to -5.6 kg.
• Semaglutide has been shown to be effective in achieving significant weight loss in diabetic patients, with a notable reduction in HbA1c levels as well 2, 2.

From the Research

Weight Loss Medications for Diabetics

• The distinction between glucose-lowering medication and weight loss medication is becoming blurred, with some newer glucose-lowering medications such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) also being used or considered for use as anti-obesity drugs 3.
• There are several FDA-approved anti-obesity medications, including phentermine, orlistat, phentermine/topiramate ER, naltrexone SR/bupropion SR, liraglutide 3.0 mg, semaglutide 2.4 mg, and tirzepatide, which can be prescribed for long-term use 4.
• Other medications, such as metreleptin and setmelanotide, are indicated for rare obesity syndromes, while medications like orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, and semaglutide are approved for non-syndromic obesity 5.

Comparison of Weight Loss Medications

• Semaglutide has been shown to be superior to liraglutide in reducing HbA1c and body weight in subjects with type 2 diabetes, with a greater proportion of subjects achieving glycaemic targets and weight loss of =5% and =10% 6.
• A systematic review comparing the effectiveness of semaglutide, liraglutide, orlistat, and phentermine for weight loss in obese individuals found that all agents presented distinct benefits, but also had side effects that necessitate tailored treatment approaches 7.
• The choice of anti-obesity medication should take into consideration the patient's clinical and biochemical profile, co-morbidities, and drug contra-indications, as well as expected degree of weight loss and improvements in cardio-renal and metabolic risk 5.