Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial

Abstract

OBJECTIVETo evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment. RESEARCH DESIGN AND METHODSIn this phase III, double-blind, randomized, placebo-controlled, two-arm, parallel-group, multicenter trial, patients aged ‡70 years were randomized to receive once-daily lixisenatide 20 mg or placebo before breakfast concomitantly with their existing antidiabetic therapy (including insulin) for 24 weeks. Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded. The primary end point was absolute change in HbA 1c from baseline to week 24. Secondary end points included change from baseline to week 24 in 2-h postprandial plasma glucose (PPG) and body weight. RESULTSA total of 350 patients were randomized. HbA 1c decreased substantially with lixisenatide (20.57% [6.2 mmol/mol]) compared with placebo (+0.06% [0.7 mmol/mol]) from baseline to week 24 (P < 0.0001). Mean reduction in 2-h PPG was significantly greater with lixisenatide (25.12 mmol/L) than with placebo (20.07 mmol/L; P < 0.0001). A greater decrease in body weight was observed with lixisenatide (21.47 kg) versus placebo (20.16 kg; P < 0.0001). The safety profile of lixisenatide in this older population, including rates of nausea and vomiting, was consistent with that observed in other lixisenatide studies. Hypoglycemia was reported in 17.6% of patients with lixisenatide versus 10.3% with placebo. CONCLUSIONSIn nonfrail older patients uncontrolled on their current antidiabetic treatment, lixisenatide was superior to placebo in HbA 1c reduction and in targeting postprandial hyperglycemia, with no unexpected safety findings.

Diabetes and Aging: Unique Considerations and Goals of Care

“…The safety of therapies in older adults with diabetes is important to consider in clinical practice to minimize polypharmacy and potential adverse side effects. Meneilly et al (25) conducted a phase III, double-blind, randomized, placebo-controlled trial (lixisenatide GetGoal-O trial) in patients ≥70 years of age with type 2 diabetes uncontrolled on their current antidiabetic treatment and evaluated the efficacy and safety of lixisenatide versus placebo on glycemic control. They concluded that “in nonfrail older patients uncontrolled on their current antidiabetic treatment, lixisenatide was superior to placebo in HbA 1c reduction and targeting postprandial hyperglycemia, with no unexpected safety findings.” In the article by Bethel et al (26), baseline data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) among participants ≥75 years of age with well-controlled type 2 diabetes and cardiovascular disease were examined.…”

Efficacy and safety of lixisenatide as add‐on therapy to basal insulin in older adults with type 2 diabetes in the GetGoal‐O Study

“…In all, 108 patients met the inclusion criteria for this subgroup analysis, of whom 53 were in the lixisenatide group and 55 were in the placebo group. Baseline demographics and characteristics were generally similar in both treatment groups (Table ) and to those in the overall study population . One difference of note was that, compared with the lixisenatide group, the placebo group had a slightly higher body mass index (BMI) at baseline, and a greater proportion of patients had a BMI ≥30 kg/m 2 (Table ).…”

“…This was a post hoc analysis of the GetGoal‐O trial (http://Clinicaltrials.gov ID NCT01798706), details of which have been published previously . GetGoal‐O was a randomized, double blind, placebo‐controlled, two‐arm, parallel‐group, multinational, multicenter clinical trial in patients aged ≥70 years.…”

“…Despite this, older adults with T2D are often excluded from clinical trials. As a consequence, guidelines for pharmacological management of these patients are generally based on data extrapolated from studies in the general population . However, diabetes in this population is often metabolically distinct from that of younger people .…”

“…The efficacy and safety of once‐daily lixisenatide (10 μg for 2 weeks, then 20 μg) in the treatment of T2D have been demonstrated in the global GetGoal Phase 3 clinical trials program, which included more than 5000 patients using a variety of background medications of OADs and/or basal insulin . In the Phase 3 GetGoal‐O trial, which specifically recruited patients aged ≥70 years, among 350 randomized patients lixisenatide added to existing antihyperglycemia therapy was superior to placebo in reducing HbA1c and in targeting postprandial hyperglycemia, and had a favorable tolerability profile …”