title: Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged ≥ 65 years) with inadequately controlled type 2 diabetes mellitus.
abstract: OBJECTIVE
  To assess safety and efficacy of saxagliptin in older patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  This was a post hoc analysis of pooled data from older patients (≥65 years of age) from five 24-week phase III trials: three studies of saxagliptin versus placebo as an add-on therapy to metformin, glyburide, or a thiazolidinedione; and two studies of saxagliptin versus placebo as monotherapy in drug-naïve patients. Separate analyses were conducted on one study of initial combination therapy with saxagliptin plus metformin versus metformin monotherapy in drug-naïve patients. The safety analysis population for the five-study pool included 428 patients ≥ 65 years of age with baseline glycated hemoglobin (HbA(1c)) 7.0% to 10.5% who received saxagliptin 2.5 or 5 mg or placebo, and for the study of initial combination therapy included 69 patients ≥ 65 years of age with baseline HbA(1c) 8.0% to 12.0% who received saxagliptin 5 mg in combination with metformin or metformin monotherapy. The primary efficacy endpoint was change from baseline HbA(1c).
  
  
  RESULTS
  In the five-study pool, the differences in the adjusted mean change from baseline HbA(1c) among older patients receiving saxagliptin versus placebo were -0.60% (95% confidence interval [CI], -0.99% to -0.21%) for saxagliptin 2.5 mg and -0.55% (-0.97% to -0.14%) for saxagliptin 5 mg; in the initial combination study, the difference was -1.22% (-2.27% to -0.17%) among older patients receiving saxagliptin 5 mg plus metformin versus metformin monotherapy. The results were generally similar in older and younger patients. Saxagliptin was well tolerated; the incidence and types of adverse events were similar for saxagliptin and comparators. Hypoglycemia was reported in 3.0% to 9.4% of patients receiving saxagliptin (0%-8.0% for comparators) and was confirmed (finger stick glucose ≤ 50 mg/dL, with associated symptoms) in 0% to 0.7% (0%-0.7% for comparators); hypoglycemic episodes did not vary by age category and did not require medical intervention.
  
  
  CONCLUSIONS
  Saxagliptin was effective and well tolerated, with a low risk of hypoglycemia, when used as monotherapy, add-on therapy, or initial combination therapy with metformin in older patients with T2DM.
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA. chetan.karyekar@bms.com
authors.forename: Chetan S
authors.initials: CS
authors.lastname: Karyekar
authors.forename: Shoba
authors.initials: S
authors.lastname: Ravichandran
authors.forename: Elsie
authors.initials: E
authors.lastname: Allen
authors.forename: Douglas
authors.initials: D
authors.lastname: Fleming
authors.forename: Robert
authors.initials: R
authors.lastname: Frederich
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D054795:Incretins / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000218:Adamantane; D004151:Dipeptides; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D008687:Metformin; D045162:Thiazolidinediones; C502994:saxagliptin; C089946:2,4-thiazolidinedione
keywords: DPP-4 inhibitor; clinical trial; dipeptidyl peptidase-4; hypoglycemia; metformin