PURPOSE: The management of hyperglycemia is challenging in older patients with type 2 diabetes owing to excess fragility and risk for adverse outcomes should hypoglycemia episodes occur. We evaluated baseline β-cell function as a potential risk factor for the development of hypoglycemia when saxagliptin or glimepiride was added in patients aged ≥65 years whose type 2 diabetes was poorly controlled on stable metformin monotherapy. METHODS: A post hoc analysis of data from the GENERATION (Efficacy and Tolerability of Saxagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes: A Randomized, Controlled Study) trial, which enrolled 720 patients aged ≥65 years, was conducted. β-Cell function was assessed using homeostasis model assessment-2%β (HOMA-2%β). FINDINGS: The percentage of patients experiencing any hypoglycemia event (ie, symptomatic event or event of plasma glucose concentration <54 mg/dL regardless of symptoms) was lower with saxagliptin compared with glimepiride (5.8% vs 34.8%). Regardless of treatment, patients with lower (median HOMA-2%β ≤39.1% [≤median]) versus higher (HOMA-2%β above median value [>median]) baseline β-cell function had a higher hypoglycemia event rate (1.27 vs 0.82 events/patient-year; adjusted incidence rate ratio [IRR] = 1.800; 95% CI, 1.501-2.159). In patients receiving glimepiride, the hypoglycemia event rate was higher in patients with baseline HOMA-2%β ≤median versus >median (2.29 vs 1.60 events/patient-year; adjusted IRR = 1.737; 95% CI, 1.439-2.097); corresponding saxagliptin hypoglycemia event rates were too low to draw meaningful conclusions (0.16 vs 0.09 events/patient-year; adjusted IRR = 2.457; 95% CI, 1.148-5.256). The association between lower β-cell function at baseline and increased prevalence of hypoglycemia was particularly strong in patients aged ≥75 years (adjusted IRR = 2.409; 95% CI, 1.686-3.442; P < 0.001), although it was also significant in patients aged 65 to <75 years old (adjusted IRR, 1.654; 95% CI, 1.339-2.043; P < 0.001). IMPLICATIONS: In patients with lower β-cell function, the addition of a sulfonylurea to a metformin regimen was associated with an increased risk for hypoglycemia compared with that in patients with higher β-cell function; low hypoglycemia event rates with the addition of saxagliptin limited equivalent assessments. These findings in older patients are especially relevant because morbidity associated with hypoglycemia is higher in this age group. ClinicalTrials.gov identifier: NCT01006603 (ClinicalTrials.gov).
RCT Entities:
PURPOSE: The management of hyperglycemia is challenging in older patients with type 2 diabetes owing to excess fragility and risk for adverse outcomes should hypoglycemia episodes occur. We evaluated baseline β-cell function as a potential risk factor for the development of hypoglycemia when saxagliptin or glimepiride was added in patients aged ≥65 years whose type 2 diabetes was poorly controlled on stable metformin monotherapy. METHODS: A post hoc analysis of data from the GENERATION (Efficacy and Tolerability of Saxagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes: A Randomized, Controlled Study) trial, which enrolled 720 patients aged ≥65 years, was conducted. β-Cell function was assessed using homeostasis model assessment-2%β (HOMA-2%β). FINDINGS: The percentage of patients experiencing any hypoglycemia event (ie, symptomatic event or event of plasma glucose concentration <54 mg/dL regardless of symptoms) was lower with saxagliptin compared with glimepiride (5.8% vs 34.8%). Regardless of treatment, patients with lower (median HOMA-2%β ≤39.1% [≤median]) versus higher (HOMA-2%β above median value [>median]) baseline β-cell function had a higher hypoglycemia event rate (1.27 vs 0.82 events/patient-year; adjusted incidence rate ratio [IRR] = 1.800; 95% CI, 1.501-2.159). In patients receiving glimepiride, the hypoglycemia event rate was higher in patients with baseline HOMA-2%β ≤median versus >median (2.29 vs 1.60 events/patient-year; adjusted IRR = 1.737; 95% CI, 1.439-2.097); corresponding saxagliptinhypoglycemia event rates were too low to draw meaningful conclusions (0.16 vs 0.09 events/patient-year; adjusted IRR = 2.457; 95% CI, 1.148-5.256). The association between lower β-cell function at baseline and increased prevalence of hypoglycemia was particularly strong in patients aged ≥75 years (adjusted IRR = 2.409; 95% CI, 1.686-3.442; P < 0.001), although it was also significant in patients aged 65 to <75 years old (adjusted IRR, 1.654; 95% CI, 1.339-2.043; P < 0.001). IMPLICATIONS: In patients with lower β-cell function, the addition of a sulfonylurea to a metformin regimen was associated with an increased risk for hypoglycemia compared with that in patients with higher β-cell function; low hypoglycemia event rates with the addition of saxagliptin limited equivalent assessments. These findings in older patients are especially relevant because morbidity associated with hypoglycemia is higher in this age group. ClinicalTrials.gov identifier: NCT01006603 (ClinicalTrials.gov).