Understanding the impact of commonly utilized, non-insulin, glucose-lowering drugs on body weight in patients with type 2 diabetes

ABSTRACT

Introduction: The majority of patients with type 2 diabetes also have obesity. Obesity increases the risk of developing diabetes and is associated with worsened glycemic control and increased morbidity and mortality in individuals with diabetes. Sustained weight loss is associated with improved glycemic control, potential for diabetes remission, and decreased medical expenditures.

Areas covered: Herein, the impact of commonly utilized, non-insulin, glucose-lowering drugs on body weight in patients with type 2 diabetes is discussed. The weight change magnitudes, mechanisms, and any within-class differences are also explored.

Expert opinion: The weight impact of diabetes medications should be considered when designing treatment regimens, especially in patients who are overweight or have obesity. Lifestyle modification is paramount for optimal diabetes management. Therapeutic regimens should ideally be designed to maximize weight loss and at least minimize or avoid weight gain. Future glucose-lowering medications should continue to offer improvement in cardiovascular risk factors, including weight, in order to be accepted into the armamentarium of diabetes therapy. Therapeutic regimens should be designed to help patients with diabetes and obesity achieve both glycemic and weight goals. Management of these disease states is expected to become increasingly integrated.

KEYWORDS:

• Body weight
• dipeptidyl peptidase-4 inhibitor
• glucagon-like peptide 1-receptor agonist
• metformin
• obesity
• pharmacotherapy
• sodium glucose cotransporter-2 inhibitor
• sulfonylurea
• thiazolidinedione
• type 2 diabetes

Article highlights

• Non-insulin, glucose-lowering medications can contribute to weight gain (sulfonylureas, TZDs), weight loss (GLP-1RAs, SGLT-2 inhibitors, metformin), or be weight neutral (DPP-4 inhibitors).

• Mechanisms for weight gain attributed to glucose-lowering medications vary among classes but may include fat accumulation, fluid retention, and/or increased insulin secretion.

• Mechanisms for weight loss include decreased hepatic gluconeogenesis, signaling satiety in the CNS, and increased glucosuria favoring a shift from carbohydrate to fat metabolism.

• Weight impact may vary within classes of medication, especially for GLP-1RAs, where semaglutide and liraglutide have been associated with greatest weight loss, and lixisenatide and albiglutide cause less, if any, clinically significant weight change.

• Therapeutic regimens should be designed to help patients with diabetes and obesity achieve glycemic and weight goals.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.