Abstract
Clinical question
Which antidiabetic drugs provide optimal weight control in patients with type 2 diabetes?
Results
Metformin reduces weight gain, and may cause weight loss, when given alone or in combination with other drugs. Pioglitazone and rosiglitazone use is associated with weight gain. Use of the glucagon-like peptide-1 (GLP-1) analogs, liraglutide and exenatide, is associated with weight loss. Dipeptidyl peptidase-4 (DPP-4) inhibitors are considered weight-neutral. Results with insulin therapy are conflicting. Insulin detemir provides weight control along with glycemic control.
Implementation
Weight gain is considered an inevitable part of good glycemic control using conventional modalities of treatment such as sulfonylureas.1
Use of metformin, weight-sparing insulin analogs such as insulin detemir, and liraglutide, should be encouraged as monotherapy, or in combination with other drugs.
Keywords: weight control, diabetes
Weight control in diabetes
Definition: Weight control is an important aspect of diabetes treatment, and can improve glycemic control and cardiovascular risk factors per se.1,2 The term “diabesity” is used to define the pathogenic relationship between diabetes and obesity.3
Incidence: Glycemic control using conventional drugs is usually associated with weight gain.3 A head-to-head comparison of various treatment modalities regarding the incidence of weight gain has not been done.
Economics: No published study has addressed the direct cost of weight gain during diabetes treatment. However, weight loss has been shown to reduce medical and pharmaceutical costs in patients with diabetes.4 Drugs which are relatively more cost-effective, such as sulfonylureas, may not end up being cheaper if they increase the overall costs of therapy, and studies are needed to address this issue.
Level of evidence: Systemic reviews, meta-analysis, randomized controlled trials, guidelines.
Search sources: PubMed, Cochrane Library, Google Scholar.
Outcomes: Both physicians and patients seek:
Minimum weight gain in patients of normal weight
Weight loss in overweight patients
Consumer summary: Patients with diabetes tend to gain weight when given antidiabetic drugs. There is good evidence that metformin, insulin detemir, and newer drugs such as liraglutide prevent weight gain when prescribed alone, or in combination with other drugs.
The evidence
Do antidiabetic drugs increase or decrease weight?
| Systematic reviews | > 10 |
| Meta-analyses | > 10 |
| Randomized controlled trials | > 100 have been published. |
Systematic reviews5,6 and meta-analysis have concluded that pioglitazone and rosiglitazone lead to weight gain. The combined use of metformin and the thiazolidinediones shows controversial results related to weight gain.
Sulfonylurea use is linked to significant weight gain.7 Addition of sulfonylureas to metformin is also associated with weight gain, but to a lesser degree, according to meta-analysis. 8 A meta-analysis has shown that a combination of sulfonylureas and insulin does not lead to weight gain.9
Metformin has been shown to reduce weight, as compared with sulfonylureas, in meta-analysis.10 Metformin, when used as cotherapy, also mitigates the weight gain seen with sulfonylureas and repaglinide.11
Alpha-glucosidase inhibitors have an insignificant effect on weight, as per a meta-analysis of 41 studies.12 A randomized controlled trial shows that voglibose coadministration can reduce the weight gain associated with pioglitazone use.13
Other meta-analysis shows that the DPP-4 inhibitors, such as vildagliptin and sitagliptin, are weight-neutral,14 while the GLP-1 analogs, ie, liraglutide and exenatide, are associated with weight loss.
Insulin detemir is the only insulin to show weight loss or reduced weight gain consistently in overweight patients in meta-analysis.15 Results with other insulin preparations are conflicting.16 Insulin glargine use causes more weight gain than Neutral Protamine Hagedorn insulin.17
The practice
Potential pitfalls
Weight control and glycemic control should be aimed for
Weight gain may mitigate the benefits achieved by glycemic control
Try to combine regimes with metformin, but keep a watch for contraindications and side effects of metformin
Avoid using a combination of medications which cause weight gain
Avoid overdosage of insulin, which may lead to weight gain by causing hypoglycemia and increased snacking.
Management
Assessment
Measure weight, waist and hip circumference, and watch for edema regularly in all patients with diabetes
Presence of edema or waist gain should prompt a review of antidiabetic, as well as other, medications.
Treatment
If possible, discontinue or replace thiazolidinediones if excessive weight gain occurs with their use, or is to be avoided
Reduce the dose of insulin, especially rapid-acting insulin if patients complain of excessive weight gain associated with hypoglycemia
Shift to insulin detemir if indicated
Add/increase the dose of metformin, to maximally tolerated levels
Use GLP-1 analogs, such as liraglutide and exenatide, if weight gain is an issue.
Footnotes
Conflict of interest: SK has received speaker fees from Novo Nordisk, sanofi-aventis, MSD, Eli Lilly, BMS, and AstraZeneca.
Date of preparation: 18th August 2010
References
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