Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes - SCALE

Aug 19, 2015
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novo Nordisk
Date Published:
08/18/2015
Original Posted Date:
08/19/2015
References

Description:

The goal of the trial was to compare the safety and efficacy of liraglutide, a glucagon-like peptide 1 (GLP-1) analog, in affecting weight loss in patients with type 2 diabetes and obesity.

Contribution to the Literature: The SCALE trial showed that in obese patients with type 2 diabetes, liraglutide 3 mg and 1.8 mg daily both achieved greater weight loss and better glycemic control at 56 weeks, compared with placebo.

Study Design

Obese patients with type 2 diabetes were randomized to receive liraglutide (3.0 mg [n = 423]), liraglutide (1.8 mg [n = 211]), or placebo (n = 212).

Inclusion criteria:

  • Overweight or obese (body mass index [BMI] ≥27.0 kg/m2)
  • Adults (age ≥18 years)
  • Stable body weight (<5 kg change in the last 3 months)
  • Type 2 diabetes (glycated hemoglobin [HbA1c] 7.0%-10.0%) treated with diet and exercise alone or in combination with 1-3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea)
  • Total number of enrollees: 846
  • Duration of follow-up: 56 weeks
  • Mean patient age: 55 years
  • Percentage female: 51%
  • Percentage diabetics: 100%

Other salient features/characteristics:

  • Mean baseline weight 106.0 kg; BMI 37.2 kg/m2 (BMI 35-39.9 = 25%, >40 = 30%)
  • Waist circumference 118 cm
  • Duration of diabetes at 7 years: HbA1c 8%
  • Known coronary artery disease 15%
  • Treatment for diabetes: Diet and exercise 12%, metformin alone 57%, metformin + sulfonylurea 21%

Principal Findings:

The primary outcome, change in body weight from baseline for liraglutide 3 mg vs. liraglutide 1.8 mg vs. placebo was -6 vs. -4.7 vs. -2.0 (p < 0.001 for both). Weight loss >5% was 54.3% vs. 40.4% vs. 21.4%, p < 0.001 for both. Weight loss >10% was 25.2% vs. 15.9% vs. 6.7%, p < 0.01 for both.

Secondary outcomes:

  • Changes in waist circumference: -6.1 vs. -4.8 vs. -2.7 cm, p < 0.001 for both
  • BMI -2.2 vs. -1.7 vs. -0.8, p < 0.001 for both
  • HbA1c -1.3 vs. -1.1 vs. -0.3, p < 0.001 for both
  • High-density lipoprotein: 4.7 vs. 4.45 vs. 1.93, p = 0.03 for liraglutide 3 mg vs. placebo, p = 0.16 for liraglutide 1.8 mg vs. placebo
  • High-sensitivity C-reactive protein: -33.51 vs. -33.34 vs. -10.45, p < 0.001

Gastrointestinal (GI) side effects, particularly nausea, vomiting, diarrhea, and constipation, were more common with liraglutide. Mean heart rate increases of 2.0/min and 2.1/min occurred with liraglutide (3.0 mg) and liraglutide (1.8 mg) vs. -1.4/min for placebo (p < 0.001 for both). No cases of acute pancreatitis were reported.

Interpretation:

The results of this trial indicate that in obese patients with type 2 diabetes, liraglutide 3 mg and 1.8 mg daily achieve greater weight loss and better glycemic control at 56 weeks, compared with placebo. The majority of patients were already on metformin. GI side effects were more common with liraglutide. These results are encouraging and suggest an important role for GLP-1 agonists in the treatment of patients with obesity and type 2 diabetes.

The increase in heart rate with liraglutide has been reported with other GLP-1 agonists as well as anti-obesity medications before. The long-term impact is unclear, but a large clinical trial powered for cardiovascular safety of liraglutide (LEADER) is ongoing.

References:

Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA 2015;314:687-699.

Keywords: Body Mass Index, Body Weight, C-Reactive Protein, Glucagon-Like Peptide 1, Hypoglycemic Agents, Metabolic Syndrome, Metformin, Obesity, Primary Prevention, Sulfonylurea Compounds, Thiazolidinediones, Weight Loss


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