Glucagon-like peptide-1 agonists have been evaluated for their effects on weight loss, blood pressure, and lipid levels. Substantial weight reduction was observed in monotherapy trials with both exenatide and liraglutide.
10,11 Table 5 shows trial results on weight loss for the most common doses of these drugs used in clinical practice. Small effects on blood pressure were seen with exenatide and liraglutide in these trials, but lipid profiles remained essentially unchanged in trials lasting 1 year or less.
Table 5.
Effects on Body Weight of Exenatide and Liraglutide in Combination With Metformin, Sulfonylurea, and Thiazolidinedione
Agent Combination Weight Loss, kg Exenatide, 10 μg twice daily10 -3.1 + Metformin13 -2.8 + Sulfonylurea18 -1.6 + Thiazolidinedione20 -1.7 + Metformin + Sulfonylurea19 -1.6 + Metformin + Thiazolidinedione20 -1.7 Liraglutide, 1.2 mg daily11 -2.1 + Metformin21 -2.6 + Sulfonylurea22 0.3 + Metformin + Sulfonylurea17 1.0 + Metformin + Thiazolidinedione23 -1.0
Table 5.
Effects on Body Weight of Exenatide and Liraglutide in Combination With Metformin, Sulfonylurea, and Thiazolidinedione
Agent Combination Weight Loss, kg Exenatide, 10 μg twice daily10 -3.1 + Metformin13 -2.8 + Sulfonylurea18 -1.6 + Thiazolidinedione20 -1.7 + Metformin + Sulfonylurea19 -1.6 + Metformin + Thiazolidinedione20 -1.7 Liraglutide, 1.2 mg daily11 -2.1 + Metformin21 -2.6 + Sulfonylurea22 0.3 + Metformin + Sulfonylurea17 1.0 + Metformin + Thiazolidinedione23 -1.0
×
Specifically, monotherapy with exenatide resulted in weight reductions of 2.8 and 3.1 kg using 5 and 10 μg twice daily, respectively, over 24 weeks.
10 Systolic blood pressure decreased by about 4 mm Hg with both doses of exenatide, and diastolic pressure decreased by about 0.8 and 2.3 mm Hg with the 5 and 10 μg doses, respectively. There was no measurable effect of exenatide on levels of total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol.
10
Monotherapy with liraglutide resulted in decreases in weight of 2.1 and 2.5 kg in patients receiving doses of 1.2 and 1.8 mg, respectively.
11 Weight loss occurred during the first 4 months of the trial and was sustained for more than 1 year. Systolic blood pressure decreased by approximately 2 and 4 mm Hg using 1.2- and 1.8-mg doses, respectively.
9 The effects of liraglutide on lipid levels were not investigated.
Substantial weight loss has also been noted when GLP-1 agonists are used in combination with metformin, a sulfonylurea, or a thiazolidinedione.
13,17-23 Data for the most common clinical doses of these combinations are shown in
Table 5. Exenatide produced essentially no effect on blood pressure or lipids in studies lasting 1 year or less.
18 However, in an open-label trial lasting 3.5 years, exenatide showed statistically significant improvements in triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol (
P<.001 for all comparisons); blood pressure was also improved.
24 These benefits were attributed to a slow, progressive weight loss of 5 to 12 kg, with the greatest benefit accruing to patients who lost the most weight.
24 In the 26-week LEAD-6 trial,
17 liraglutide consistently decreased systolic blood pressure by about 2 to 4 mm Hg and triglyceride level by about 36 mg/dL.
Gastric adverse effects of GLP-1 agonists are discussed by Dr Gavin elsewhere in this
JAOA supplement (“Initiating a Glucagon-like Peptide-1 Receptor Agonist in the Management of Type 2 Diabetes Mellitus”
25). The major adverse effects are nausea, vomiting, and diarrhea.
26,27 The incidence of these effects increases as the dose is increased and varies little when the drugs are used as monotherapy or as combination therapy with other, oral antidiabetic agents. Exenatide monotherapy was associated with nausea (in 8% of patients) and vomiting (in 4% of patients).
26 In combination with metformin or a sulfonylurea—and subtracting the placebo control—the incidences of nausea, vomiting, and diarrhea with exenatide were 26%, 9%, and 7%, respectively.
26 The incidences of adverse effects with liraglutide are similar to those observed with exenatide.
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