Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

Abstract

Glucagon-like peptide-1 (GLP-1) has been evaluated for use in the treatment of type 2 diabetes mellitus (T2DM) due to its role in glucose regulation. Four GLP-1 receptor agonists (RAs) are currently indicated for T2DM in the USA. Exenatide and liraglutide are short-acting and require twice-daily and daily dosing, respectively. Two longer acting agents, exenatide long-acting release (LAR) and albiglutide, were formulated to allow for once-weekly dosing. All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first-and secondline diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin. Greater glycemic control was seen with liraglutide compared with the other GLP-1 treatment options; however, the two long-acting agents were superior to exenatide twice daily. All agents were well tolerated with most adverse events being mild or moderate in nature. The most common adverse event was transient nausea which typically resolved 4-8 weeks after treatment initiation. Long-acting agents had lower rates of nausea but an increased incidence of injection site reactions. Trials have suggested GLP-1 RAs may improve cardiovascular risk factors including blood pressure, lipid parameters and inflammatory markers. Future trials are needed to confirm the clinical outcomes of these agents. Overall, GLP-1 RAs will provide benefit for patients with T2DM intolerable to or not reaching glycemic goals with first-line agents, especially in patients in need of weight loss.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

“…Liraglutide improves glycaemic control when used as monotherapy or add-on therapy 239,241,247,248 (see Supplementary information S4 (table)). Compared with glimepiride 8 mg daily, liraglutide 1.2-1.8 mg daily monotherapy resulted in greater reductions in HbA 1c from an average baseline of 8.3% (glimepiride −0.6%, liraglutide 1.2 mg −0.9% and liraglutide 1.8 mg −1.1%; treatment difference for liraglutide 1.2 mg −0.31%, 95% CI −0.54% to −0.08%, P = 0.008; treatment difference for liraglutide 1.8 mg −0.60%, 95% CI −0.83% to −0.38%, P <0.0001).…”

“…Exenatide once weekly monotherapy has been noninferior to metformin, superior to sitagliptin and similar to pioglitazone with regard to HbA 1c reduction in RCTs at 26 weeks 239,258 . Addition of exenatide once weekly to metformin is more effective for the achievement of glucose control than addition of either sitagliptin or pioglitazone to metformin 218,239 .…”

“…Exenatide (twice daily) significantly reduces measures of glycaemic control when used as monotherapy or add-on therapy (see Supplementary information S4 (table)) [239][240][241][242][243] . A meta-analysis 244 of RCTs in which exenatide was an add-on to existing metformin therapy for 16-30 weeks showed that exenatide lowers HbA 1c by 0.8% from an average baseline of 8.1 ± 0.6%.…”

“…Exenatide once weekly reduces HbA 1c , FPG and postprandial glucose when used as monotherapy or add-on treatment 218,239,241,258 . Exenatide once weekly monotherapy has been noninferior to metformin, superior to sitagliptin and similar to pioglitazone with regard to HbA 1c reduction in RCTs at 26 weeks 239,258 .…”

Real-world comparison of treatment patterns and effectiveness of albiglutide and liraglutide

“…For patients who are unable to achieve glycemic goals with metformin alone, one or more additional antidiabetic agents are used in later lines of treatment, including oral and injectable therapies. Agents that target glucagonlike peptide-1 (GLP-1) may be recommended among several treatment choices in the second or later lines of treatment, and they may also be used as first-line treatment in patients in whom metformin is contraindicated or not tolerated [1,2].…”