Impact of weight gain on outcomes in type 2 diabetes

Abstract

Background:

The majority of patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Obesity is a significant risk factor for increased morbidity and mortality in people with T2DM, and increased weight has been shown to worsen glycemic control and increase the risk of diabetes progression.

Methods:

A search was conducted of the National Library of Medicine (PubMed) for articles published from 1990 to 2009 about the treatments of T2DM, relationship between T2DM and weight gain, obesity-related comorbidities of T2DM, and T2DM therapies associated with increased weight. Reference lists of retrieved articles were reviewed for additional publications.

Findings:

Results from large, prospective clinical trials have shown that weight reduction significantly improves glycemic control and blood pressure in T2DM patients and lowers the risk of progression of T2DM as well as CV disease and cancer. Treatment-related weight gain is a side effect of many oral antidiabetes agents and insulin. The thiazolidinediones (TZD), sulfonylureas, and glinides are associated with weight gain. Despite the weight gain, TZDs also redistribute fat from the central to peripheral compartments, which may lead to a beneficial effect on insulin resistance. Among insulin products, the basal insulin analog detemir is typically associated with a smaller weight increase than human insulin and insulin analog preparations, including glargine, biphasic, and prandial insulin regimens. Alpha-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors are weight neutral, whereas glucagon-like peptide1-R agonists and metformin are associated with weight loss.

Discussion:

An effective approach to management of the obese patient with diabetes is to communicate the significant benefits of a 1 kg reduction in body weight or prevention of weight gain on glycemic control and reduced morbidity and mortality.

Limitation:

This article is based on an extensive literature review rather than the prospective studies needed to define further the effect of weight gain on the management of T2DM.

Conclusion:

Weight management should be an integral part of a T2DM treatment strategy that includes selecting oral antidiabetes medications and insulin products that are weight beneficial.

Key words::

• Antidiabetic drugs
• Cardiovascular
• Morbidity
• Mortality
• Obesity
• Type 2 diabetes
• Weight gain

Transparency

Declaration of financial/other relationships

S.A.R. has disclosed that he has been a member of an advisory board for Novo Nordisk; a consultant to Novo Nordisk; received grants or has grants pending from Eli Lilly and Novo Nordisk; and a member of speakers bureaus for Eli Lilly and Novo Nordisk. G.D. has been a consultant for Life Scan, Sanofi-Aventis, and Eli Lilly; a member of speakers bureaus for Bioton and Servier; and received payment for the development of educational presentations for NovoNordisk. J.V. has served on advisory boards for Lilly Industries, Sanofi-Aventis, Merck, Takeda Industries, Novo Nordisk, Bristol-Myers Squibb, Johnson & Johnson, and Abbott Diabetes Care; received grants or has grants pending from Lilly Industries and Novo Nordisk; received payment for lectures from Lilly Industries, Daiichi-Sankyo, Novo Nordisk, and Bristol-Myers Squibb; and received grants for delivering presentations at meetings from Sanofi-Aventis, GlaxoSmithKline, and Boehringer Ingelheim. K.K. has received a grant from HTA; been a member of advisory boards for Novo Nordisk, Eli Lilly, Merck, Bristol-Myers Squibb, and Roche; and received payment for delivering presentations for Novo Nordisk, Eli Lilly, Sanofi-Aventis, Novartis, and Merck. M.K. has been a member of an advisory board for Novo Nordisk. R.J.L. has received payment from his institution from Tropvacc BV for travel to meetings, board membership, consulting, expert testimony, and delivering lectures.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

Editorial support for this manuscript was provided by Richard S. Perry, PharmD, and was funded by Novo Nordisk.