Efficacy and Safety of Ideglira in Older Patients With Type 2 Diabetes

Ildiko Lingvay, MD; Yehuda Handelsman, MD; Sultan Linjawi, MBBS; Tina Vilsbøll, MD; Natalie Halladin, PhD; Kristina Ranc, MSc; Andreas Liebl, MD

Disclosures

Endocr Pract. 2019;25(2):144-155. 

In This Article

Abstract and Introduction

Abstract

Objective: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years.

Methods: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1–receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V).

Results: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, −1.0% [−1.5; −0.6]95% confidence interval [CI], −0.8% [−1.0; −0.5]95% CI, and −0.9% [−1.3; −0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 [0.2; 1.6]95% CI [P= .242]; 0.3 [0.1; 0.5]95% CI [P<.001], and 11.8 [3.3; 42.8]95% CI [P<.001] for DUAL II, V, and III, respectively).

Conclusion: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall.

Introduction

By 2050, the prevalence of diabetes is predicted to increase 2-fold in patients aged 65 to 74 years and 4-fold in patients aged ≥75 years.[1] Older patients are sometimes excluded from clinical trials over concerns about polypharmacy, multiple comorbidities, and investigators' preferences.[2] However, with people living longer, evidence is needed about the efficacy and safety of medications in the older population as well.[2]

Good glycemic control while minimizing side effects is key to managing type 2 diabetes (T2D).[3,4] However, when intensive therapy is considered riskier in older or frail patients, glycemic targets may be relaxed.[4] An increased hypoglycemia risk is particularly significant in older patients, as they are likely to have inadequate compensatory mechanisms.[5] One study has shown a 2-fold increase in the incidence of falls in older T2D patients who experience hypoglycemia versus those who do not.[6] Severe hypoglycemia is associated with an increased risk of cardiovascular events[7] and a 2-fold increase in the risk of developing dementia.[8] It remains to be determined whether these associations are causal or common markers of frailty. Conversely, chronic hyperglycemia is associated with lower cognitive function in diabetes patients.[9] T2D therapy must therefore provide appropriate glycemic control while minimizing the risk of hypoglycemia in older patients.[10]

For some patients, one treatment option is the combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA).[3] IDegLira is a fixed-ratio combination of insulin degludec (degludec), a once-daily basal insulin with an ultra-long duration of action that lowers fasting plasma glucose (FPG),[11] and liraglutide, a once-daily analogue of human GLP-1[12] that reduces both post-prandial glucose excursions and FPG.[12] IDegLira has previously been shown to improve glycemic control, with low hypoglycemia rates, effective body-weight management, and minimal gastrointestinal side effects.[13–19] The goal of this work was to evaluate the risk-benefit ratio of IDegLira in patients ≥65 years of age.

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