Efficacy and Safety of Continuing Sitagliptin when Initiating Insulin Therapy in Subjects with Type 2 Diabetes Mellitus

Abstract

DPP-4 inhibitors (DPP-4is) are often discontinued with initiation of insulin therapy but the impact of this discontinuation on efficacy and hypoglycemia has not been studied. In this double-blind trial the safety and efficacy of initiating insulin while continuing sitagliptin (SITA) was evaluated. Eligible patients had inadequately controlled T2DM on metformin (MET, ≥ 1500 mg/day) in dual or triple combination therapy with a DPP-4i and/or sulfonylurea. Those on MET + SITA (100 mg/day) directly entered the trial; all others were switched to MET + SITA and stabilized during a run-in period. Subjects were randomized to continuing SITA or discontinuing SITA and switching to matching placebo, with both groups initiating insulin (LANTUS®), which was titrated based on fasting glucose. 746 subjects (mean A1C 8.8%, disease duration 10.6 years) were randomized. After 30 weeks, continuing SITA was superior to discontinuing SITA in reducing A1C (p<0.001). Patients who continued SITA had a lower event rate of documented symptomatic hypoglycemia (blood glucose ≤70 mg/dL) and daily insulin dose compared to patients who discontinued SITA. Summary adverse event measures and change in body weight (week 30) were similar in the 2 treatment groups. In summary, with the initiation of insulin therapy, continuation of SITA resulted in superior glycemic efficacy and less documented symptomatic hypoglycemia.Change from Baseline in A1C (%) aTreatmentLS Mean (95% CI)Difference in LS Means (95% CI)SITA, n= 373-1.88 (-1.98, -1.78)-0.46 (-0.58, -0.34)PBO, n= 370-1.42 (-1.52, -1.32)Event Rate of Documented Symptomatic Hypoglycemia (Blood Glucose ≤70 mg/dL) b, cTreatmentEvent Rate (95% CI)Event Rate Ratio (95% CI)SITA, n= 3711.55 (1.22, 1.96)0.73 (0.54, 0.98)PBO, n= 3702.12 (1.70, 2.66)Total Daily Insulin Dose (Units) a, dTreatmentLS Mean (95% CI)Difference in LS Means (95% CI)SITA, n= 36553.2 (48.5, 58.0)-8.0 (-14.6, -1.5)PBO, n= 36761.3 (56.5, 66.0)a Analyzed using a longitudinal data analysis modelb Analyzed using a negative binominal regression modelc Two subjects (both in the sitagliptin group) were not included in the analysis due to a missing value of a model covariate (race)d 11 subjects did not have post baseline insulin dose data Disclosure R. Roussel: Advisory Panel; Self; AbbVie Inc., Abbott, Eli Lilly and Company, Sanofi, Novo Nordisk A/S, AstraZeneca. Speaker's Bureau; Self; Servier. Consultant; Self; Bayer AG. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Amgen Inc., Sanofi, Novo Nordisk A/S, Danone Research. Stock/Shareholder; Self; Iriade. Advisory Panel; Self; Physiogenex S.A.S.. S. Duran-Garcia: None. Y. Zhang: None. S. Shah: Employee; Self; Merck & Co., Inc. C. Darmiento: Employee; Self; Merck & Co., Inc. R. Shankar: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; NGM Biopharmaceuticals. E.A. O'Neill: Employee; Self; Merck & Co., Inc. G.T. Golm: Employee; Self; Merck & Co., Inc. R.L. Lam: Employee; Self; Merck & Co., Inc. I. Gantz: Employee; Self; Merck Sharp & Dohme Corp. K.D. Kaufman: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc..

Diabetes mellitus in complex older patients

“…Navíc u křehkých, zčásti nebo zcela ne soběstačných diabetiků, je to jednoduché, v praxi dobře realizovatelné léčebné schéma, které zajistí cílovou kom penzaci diabetu (zaměřenou v tomto období zejména na potlačení akutních symptomů) i u této skupiny dia betiků. To potvrzují i závěry 30týdenní randomizované studie CompoSIT I [17], kam byli zařazeni diabetici 2. typu s průměrným věkem 58,6 let, u kterých bylo nutné inten zifikovat antidiabetickou léčbu (dosud užívali metformin a sitagliptin). Při kombinaci s bazálním analogem glargin dosáhli pacienti většího poklesu HbA 1c bez zvýšení rizika hypoglykemie.…”

Cost‐effectiveness of intensification with sodium‐glucose co‐transporter‐2 inhibitors in patients with type 2 diabetes on metformin and sitagliptin vs direct intensification with insulin in the United Kingdom

“…Although limited real‐world evidence exists at this stage, trial results suggest that this type of combination therapy may be an appropriate pre‐insulin intensification option. Additional recent evidence has suggested that remaining on sitagliptin when initiating insulin provides clinical benefit …”

“…Additional recent evidence has suggested that remaining on sitagliptin when initiating insulin provides clinical benefit. 19 Although clinical trials have established the clinical benefits of sitagliptin plus SGLT2 inhibitors, and thereafter sitagliptin plus insulin, the economic impact of this treatment pathway is still unknown for healthcare systems and payers. Therefore, this study sought to evaluate the long-term cost-effectiveness of intensification with SGLT2 inhibitors compared with intensification with NPH insulin while continuing sitagliptin therapy in a UK population with T2D not at goal on metformin and sitagliptin.…”