Glimepiride carries added hypoglycaemia risk in certain elderly patients with T2D
The sulfonylurea glimepiride may pose an increased risk of hypoglycaemia in a subgroup of elderly type 2 diabetes (T2D) patients with lower β-cell function when added to a metformin regimen, according to a post-hoc analysis of data from the GENERATION* trial.
“In light of our observations, which show a higher hypoglycaemia event rate in patients with low baseline β-cell function who received glimepiride, judicious use of sulfonylureas is warranted in individuals who have poor β-cell function,” the investigators said.
During the 52-week treatment period, hypoglycaemia events occurred with greater frequency in the glimepiride/metformin treatment arm than in the saxagliptin/metformin arm (34.8 vs 5.8 percent). Hypoglycaemia was defined as a symptomatic event or an event of plasma glucose concentration <54 mg/dL regardless of symptoms. [Clin Ther 2016;38:2578–2588]
Of note, the hypoglycaemia event rate was higher in the subgroup of patients with lower baseline β-cell function than in the subgroup of those with higher baseline β-cell function, irrespective of treatment (1.27 vs 0.82 events/patient-year; adjusted incidence rate ratio [IRR], 1.800; 95 percent CI, 1.501 to 2.159). β-Cell function was assessed using homeostasis model assessment-2%β (HOMA-2%β; median value, 39.1 percent).
Glimepiride contributed to an increased risk of hypoglycaemia in the subgroup of patients with HOMA-2%β ≤median (2.29 vs 1.60 events/patient-year in the subgroup of patients with HOMA-2%β >median; adjusted IRR, 1.737; 1.439 to 2.097).
On the other hand, the corresponding saxagliptin hypoglycaemia event rates were too low (0.16 vs 0.09 events/patient-year; adjusted IRR, 2.457; 1.148 to 5.256), limiting equivalent assessments.
The association between lower β-cell function and increased hypoglycaemia prevalence was especially pronounced in the ≥75 years age group (adjusted IRR, 2.409; 1.686 to 3.442; p<0.001) but was also significant in the 65 to <75 years age group (adjusted IRR, 1.654; 1.339 to 2.043; p<0.001).
The GENERATION cohort included in the current analysis consisted of 285 elderly T2D patients in the glimepiride-metformin arm and 289 in the saxagliptin-metformin arm. Of these, 276 had HOMA-2%β ≤median (mean age 73 years; 64 percent male) and 275 had HOMA-2%β >median (mean age 72 years; 57 percent male).
“These findings in older patients are especially relevant because morbidity associated with hypoglycaemia is higher in this age group,” the investigators said. “When selecting an oral antidiabetes agent for use in the elderly, the assessment of β-cell function may offer insight on the risk for hypoglycaemia and guide the clinician’s decision-making process.”
They noted that saxagliptin might be an appropriate treatment option for many elderly patients as the drug had demonstrated efficacy and tolerability in patients with T2D aged ≥65 years when used as either monotherapy or add-on therapy.
* Efficacy and Tolerability of Saxagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes: A Randomized, Controlled Study