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. 2018 Apr;64(4):295.

Sulfonylurea treatment in type 2 diabetes

Kirstin Bester 1, Joey Ton 2, Christina Korownyk 3
PMCID: PMC5897073  PMID: 29650607

Clinical question

Does treating type 2 diabetes with sulfonylureas affect mortality or cardiovascular (CV) events?

Bottom line

There is a lack of evidence that sulfonylureas reduce CV events or mortality in patients with type 2 diabetes. If anything, sulfonylureas potentially increase CV harm.

Evidence

  • Most RCTs of sulfonylureas versus placebo studied hemoglobin A1c (HbA1c) level, not patient outcomes.1–3

  • The largest RCT for outcomes (N = 409) lasted about 5 years and compared tolbutamide with placebo4,5:
    • -Both all-cause mortality (14.7% vs 10.2%) and myocardial infarction (13.7% vs 10.7%) were non-significant.
    • -There was a statistically significant increase in CV mortality (12.7% vs 4.9%; number needed to harm [NNH] = 13).
    • -Limitations were possible randomization imbalance, smoking not included in baseline characteristics, and use of a first-generation sulfonylurea.

  • An RCT (N = 304) over 5 years examined patients with coronary artery disease with a mean HbA1c level of 7.6% and compared glipizide with metformin.6 Glipizide increased composite CV events (35% vs 25%, NNH = 10).

  • An RCT (N = 2895) over 4 years (mean HbA1c level of 7.4%) compared glyburide with metformin.7 Differences in all-cause mortality (2.2% vs 2.1%) and total CV events (2.9% vs 4.0%) were non-significant. However, about 40% withdrew after randomization.

  • An RCT (N = 3028) of about 5 years compared sulfonylureas with pioglitazone and found no difference in CV events when these were added to metformin.8

  • A study of sulfonylureas versus dipeptidyl peptidase 4 inhibitors, both added to metformin, reported CV events as adverse events (3.4% vs 1.5%, NNH = 53).9

  • Studies comparing sulfonylureas with other agents were underpowered to find a difference in outcomes.10

Context

  • A systematic review of observational studies reported increased CV risk with sulfonylureas; however, multiple confounders limited the conclusion.11

  • The UK Prospective Diabetes Study is often cited to support sulfonylureas, but it is confounded by insulin use.12

  • Sulfonylureas increase the risk of hypoglycemia and weight gain.13 Hypoglycemic risk increases with renal impairment and increasing doses.13

Implementation

The primary cause of death in patients with diabetes is CV disease.14 Sulfonylureas have been recommended as second-line treatment after metformin owing to evidence for improved glycemic control and low cost. Newer agents have shown evidence of CV benefit in patients with diabetes (most with CV disease), but are much more expensive and long-term effects are uncertain.15,16

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

Competing interests

None declared

The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

Cet article se trouve aussi en français à la page 296.

References

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