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Incretin Therapies Lower Cardiovascular Risk Score

August 2012, Vol 5, No 5, Special Issue ADA 2012 Highlights - Cardiometabolic Health
Wayne Kuznar

Three incretin-based therapies—exenatide, liraglutide, and sita­gliptin—are associated with a reduction in cardiovascular (CV) risk scores, “an effect more clearly observed in patients using glucagon-like peptide-1 agonists,” said Christopher J. Smith, MD, Department of Diabetes and Endocrinology, Glasgow Royal Infirmary, Scotland, during the 2012 ADA annual meeting.

Incretin-based therapies are not simply “glucocentric” but also confer benefits with respect to weight control and possibly blood pressure (BP) reduction, Dr Smith said.

Dr Smith presented the results of a planned observational analysis of the relative CV risk and benefit of these agents in routine care in a university hospital–based diabetes center.

Dr Smith and his colleagues analyzed the effect of exenatide, liraglutide, and sitagliptin on hemoglobin (Hb) A1c level, weight, systolic BP, and lipid profile over 12 months. CV risk was calculated with the United Kingdom Prospective Diabetes Study (UKPDS) calculator, using a fixed-effects model that corrected for sex, age, diabetes duration, heart rhythm, and smoking status. The UKPDS risk engine is a validated CV risk assessment tool for patients with type 2 diabetes.

“The benefits of exenatide and lira­glutide were slightly better than for sitagliptin,” said Dr Smith.

In 102 patients, exenatide lowered the mean HbA1c level from 9.41% to 9.08% and reduced weight from 110.35 kg to 105.82 kg. Systolic BP was unchanged (134.76 mm Hg at baseline vs 134.11 mm Hg) at 12 months. The UKPDS risk score for coronary heart disease (CHD) was lowered from 18.5% to 16.3%.

A total of 30 patients used a combination of insulin and exenatide. The mean daily insulin dosage in patients receiving exenatide declined from 83.1 U to 77.5 U.

In 97 patients, liraglutide lowered the mean HbA1c level from 9.94% to 9.42%, weight from 107.97 kg to 104.07 kg, and systolic BP from 138.36 mm Hg to 134.84 mm Hg. The UKPDS risk for CHD declined from 22.4% to 20.2%.

A total of 42 patients used an insulin and liraglutide combination. The mean daily insulin dosage was reduced from 101.0 U to 94.7 U.

In 102 patients, sitagliptin lowered the HbA1c level from 9.22% to 8.95% at 12 months (a change that was not statistically significant) and had no effect on weight (93.30 kg to 92.72 kg) or systolic BP (137.03 mm Hg to 139.81 mm Hg). The UKPDS risk score decreased from 18.5% to 17.3%.

There were 12 patients who used a combination of insulin and sitagliptin. In these patients, daily insulin dosage increased significantly, from 62.8 U to 76.0 U.

“The reductions in the UKPDS risk scores are signals that perhaps we’re doing the right thing for our patients,” said Dr Smith.

Because the data for this analysis came from a clinic database, “it’s not accounting for variables like compliance,” he said.

Key Findings

  • Liraglutide lowered HbA1c level, weight, systolic BP, CV risk score, and insulin dosage
  • Exenatide lowered HbA1c level, weight, and CV risk score
  • Sitagliptin lowered HbA1c level (nonsignificantly) and CV risk score, but the effect of this agent on weight was neutral.
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Last modified: September 26, 2012
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