What is the effect of Glucagon-like peptide-1 (GLP-1) on weight loss in patients with diabetes?

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Last updated: May 14, 2025View editorial policy

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From the Guidelines

GLP-1 receptor agonists, such as semaglutide and tirzepatide, are the most effective medications for weight loss in people with diabetes, producing a significant reduction in body weight and improving glycemic control, as recommended by the latest guidelines 1. When considering weight loss with GLP-1 in the setting of diabetes, it is essential to prioritize medications with a beneficial effect on weight, such as GLP-1 receptor agonists, which have been shown to produce a mean weight loss of 5-15% over 6-12 months 1. Some key points to consider when using GLP-1 receptor agonists for weight loss in people with diabetes include:

  • Semaglutide is particularly effective, with weekly injections starting at 0.25mg and gradually increasing to 1-2mg for diabetes or up to 2.4mg for weight management 1
  • Tirzepatide, a combined glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, has also been shown to produce significant weight loss, with a mean weight change of up to −20.9% compared with placebo in obese adults without diabetes over 72 weeks 1
  • GLP-1 receptor agonists work by slowing gastric emptying, increasing satiety, and reducing appetite through central nervous system effects, and also improve glycemic control by stimulating insulin secretion and suppressing glucagon 1
  • Side effects typically include nausea, vomiting, and diarrhea, which often improve with time, and regular monitoring is important, with dose adjustments needed based on response and tolerability 1
  • These medications are generally well-tolerated but contraindicated in patients with personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 1 It is also important to note that weight management pharmacotherapy should be considered for people with diabetes and overweight or obesity, along with lifestyle changes, and that the preferred pharmacotherapy should be a GLP-1 receptor agonist or dual GIP and GLP-1 receptor agonist, such as semaglutide or tirzepatide, especially considering their added weight-independent benefits, such as glycemic and cardiometabolic benefits 1.

From the Research

Weight Loss with GLP-1 in Diabetes

  • Weight loss is a key aspect of managing diabetes, and GLP-1 receptor agonists have been shown to be effective in achieving this goal 2, 3, 4.
  • GLP-1 receptor agonists work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 2.
  • Studies have demonstrated that GLP-1 receptor agonists can lead to significant weight loss, with some agents showing greater efficacy than others 2, 3, 4.
  • The use of GLP-1 receptor agonists for weight loss is not limited to patients with diabetes, as they have also been approved for weight management in non-diabetic individuals 3.

Mechanisms of Action

  • GLP-1 receptor agonists have several mechanisms of action that contribute to their weight-loss effects, including:
    • Augmentation of hyperglycemia-induced insulin secretion
    • Suppression of glucagon secretion
    • Deceleration of gastric emptying
    • Reduction in calorie intake and body weight 2
  • These mechanisms work together to promote weight loss and improve glycemic control in patients with diabetes.

Clinical Evidence

  • numerous studies have demonstrated the efficacy of GLP-1 receptor agonists for weight loss in patients with diabetes 2, 3, 4.
  • A review of the literature found that GLP-1 receptor agonists can provide significant weight loss, as well as improvements in glycemic control and cardiovascular risk factors 4.
  • Another study found that GLP-1 receptor agonists can be used in combination with lifestyle modifications to achieve greater weight loss and improvements in glycemic control 5.

Comparison to Other Weight-Loss Strategies

  • Lifestyle modifications, such as diet and exercise, are also effective for weight loss and can be used in combination with GLP-1 receptor agonists 5, 6.
  • A review of the literature found that the most effective weight-loss intervention is one that includes a moderately reduced-calorie diet, increased physical activity, and the use of behavior strategies to facilitate adherence 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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