Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Barzilai, Nir; Guo, Hua; Mahoney, Erin; Caporossi, Suzanne; Golm, Gregory T.; Langdon, Ronald B.; Williams-Herman, Debora; Kaufman, Keith D.; Amatruda, John M.; Goldstein, Barry J.; Steinberg, Helmut O.

doi:10.1185/03007995.2011.568059

Cited by 123 publications

(83 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings were echoed in a review of the World Health Organization Clinical Trials Registry Platform where of the 440 studies examining type 2 diabetes therapies, nearly 66% excluded individuals based on an arbitrary upper age limit (3). This worrisome evidence gap has led to the question of whether it is sound clinical practice to extrapolate the findings derived from type 2 diabetes (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Two meta-analyses suggested that the DPP-4 inhibitors are associated with reduced CV risk (23,24).…”

Section: Discussionmentioning

confidence: 99%

“…Two meta-analyses suggested that the DPP-4 inhibitors are associated with reduced CV risk (23,24). Importantly, however, these data were obtained predominantly from relatively small and/or short-term investigations (18,19,30), systematic reviews (21,28,29), and pooled analyses (20,22,(25)(26)(27)31,32) in by-and-large younger and healthier study participants with very limited, and generally unadjudicated, CV safety information.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

Leiter

Teoh²,

Braunwald

et al. 2015

Diabetes Care

View full text Add to dashboard Cite

OBJECTIVETo examine the safety and cardiovascular (CV) effects of saxagliptin in the predefined elderly ( ‡65 years) and very elderly ( ‡75 years) subpopulations of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESEARCH DESIGN AND METHODSIndividuals ‡40 years (n = 16,492; elderly, n = 8,561; very elderly, n = 2,330) with HbA 1c ‡6.5% (47.5 mmol/mol) and £12.0% (107.7 mmol/mol) were randomized (1:1) to saxagliptin (5 or 2.5 mg daily) or placebo in a double-blind trial for a median follow-up of 2.1 years. RESULTSThe hazard ratio (HR) for the comparison of saxagliptin versus placebo for the primary end point (composite of CV mortality, myocardial infarction, or ischemic stroke) was 0.92 for elderly patients vs. 1.15 for patients <65 years (P = 0.06) and 0.95 for very elderly patients. The HRs for the secondary composite end points in the entire cohort, elderly cohort, and very elderly cohort were similar. Although saxagliptin increased the risk of hospitalization for heart failure in the overall saxagliptin population, there was no age-based treatment interaction (P = 0.76 for elderly patients vs. those <65 years; P = 0.34 for very elderly patients vs. those <75 years). Among saxagliptin-treated individuals with baseline HbA 1c ‡7.6% (59.6 mmol/mol), the mean change from baseline HbA 1c at 2 years was 20.69%, 20.64%, 20.66%, and 20.66% for those ‡65, <65, ‡75, and <75 years old, respectively. The incidence of overall adverse events (AEs) and serious AEs was similar between saxagliptin and placebo in all cohorts; however, hypoglycemic events were higher for saxagliptin versus placebo regardless of age. CONCLUSIONSThe SAVOR-TIMI 53 trial supports the overall CV safety of saxagliptin in a robust number of elderly and very elderly participants, although the risk of heart failure hospitalization was increased irrespective of age category. AEs and serious AEs as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients.Estimates place the global prevalence of diabetes in individuals between 60 and 79 years old at ;19%, with the number of these individuals projected to almost double by 2035 (1). Despite ongoing emphasis on the importance of practicing evidencebased medicine (2), older patients have been underrepresented in type 2 diabetes

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

Leiter

Teoh²,

Braunwald

et al. 2015

Diabetes Care

View full text Add to dashboard Cite

show abstract

“…In this placebocontrolled, 24-week study, sitagliptin treatment (100 or 50 mg, depending on renal function) significantly and rapidly improved glycaemic measures (reductions in HbA 1c from 0.5% to 1.6%, depending on baseline levels), and was well tolerated with no adverse episodes of hypoglycaemia in patients aged > 65 years with T2DM without severe RI [96].…”

Section: Elderly Patientsmentioning

confidence: 91%

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

Scheen¹

2012

Diabetes & Metabolism

174

124

View full text Add to dashboard Cite

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA 1c reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA 1c reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA 1c when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA 1c and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-tohead trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials. Keywords:Clinical trial-DPP-4 inhibitor; Alogliptin; Linagliptin; Saxagliptin; Sitagliptin; Vildagliptin; Type 2 diabetes mellitus; Review Résumé Les inhibiteurs de la DPP-4 dans le traitement du diabète de type 2 : revue critique des essais cliniques contrôlés.Les inhibiteurs de la dipeptidylpeptidase-4 (DPP-4) offrent de nouvelles options pour le traitement du diabète de type 2. Des comparaisons directes avec d'autres médicaments antidiabétiques chez des patients naïfs de tout traitement ont démontré que les inhibiteurs de la DPP-4 étaient un peu moins puissants pour diminuer ...

show abstract

“…Due to their favorable safety profile, especially in terms of reduced hypoglycemia, DPP-4 inhibitors are pro bably the only oral glucose-lowering agents for which some evidence from dedicated randomized clinical trials in patients aged ≥65 years and/or with moderate to severe renal impairment has been published over the last few years. 3,19,[32][33][34][35][36][37][38][39][40] One of these studies, a randomized, placebocontrolled trial in 133 patients with type 2 diabetes (HbA1c 7%-10%) and severe renal impairment (eGFR <30 mL/min per 1.73 m 2 ) showed that adding linagliptin (5 mg/day) to existing background therapy resulted in a significantly greater reduction of HbA1c at 12 weeks 36 which was maintained at 1 year (P<0.0001 vs baseline). In linagliptin-treated patients the incidence of adverse events and severe hypoglycemia was similar to the placebo group.…”

Section: Discussionmentioning

confidence: 99%

“…2,14,15,17 Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged in recent years as a class of oral glucose-lowering agents suitable for elderly patients, since they are generally well tolerated, have a low risk for hypoglycemia and lack significant drug interactions. 2,14,18,19 inhibitors stimulate the release of insulin in a glucose-dependent manner by counteracting the inactivation of incretins. 18,20 Linagliptin is a potent, long-acting DPP-4 inhibitor approved for the treatment of type 2 diabetes mellitus as monotherapy or as combination therapy with other oral antidiabetic agents or insulin.…”

Section: Introductionmentioning

confidence: 99%

Linagliptin is associated to increased treatment adherence and satisfaction in elderly outpatients with diabetes and advanced chronic kidney disease

et al. 2016

View full text Add to dashboard Cite

The treatment of diabetes in frail elderly patients with decreased renal function is challenging and insufficiently supported by evidence. Due to their good tolerability and low hypoglycemic risk, oral dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a reasonable option for glycemic control in the elderly. The aim was to evaluate the efficacy and safety of linagliptin, a long acting, oral DPP-4 inhibitor with a predominantly nonrenal elimination route, in elderly patients with severe chronic kidney disease (CKD). This was a retrospective, observational study in outpatients with type 2 diabetes and advanced-stage CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m 2 ) referring to a diabetes clinic in Italy. Patients were switched from basal insulin to oral linagliptin 5 mg once daily and observed for 14 months. Assessed variables included glycemic control (HbA1c target, 7.5%-8.0%), adherence to treatment (Morisky questionnaire) and patient satisfaction (diabetes treatment satisfaction questionnaire). Adverse events, including hypoglycemic episodes, were also recorded. Thirty patients [mean (±standard deviation) age 70.2 (±8.2) years, HbA1c 7.6% (±0.3), fasting blood glucose 173.9 (±23.5) mg/dL] with type-2 diabetes and advanced CKD were included. The switch to linagliptin did not affect significantly glycemic control, was well tolerated and associated with a reduction in hypoglycemic episodes. Adherence to treatment was better with linagliptin than basal insulin and patient satisfaction significantly improved after switching. Linagliptin appears as a valid option for glycemic control in elderly diabetes patients with severe CKD in treatment with low-dose insulin. However adequately designed longterm studies are needed to confirm these findings.

show abstract

Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Abstract: In this study, sitagliptin treatment significantly and rapidly improved glycemic measures and was well tolerated in patients aged ≥ 65 years with type 2 diabetes.

Cited by 123 publications

References 25 publications

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

Linagliptin is associated to increased treatment adherence and satisfaction in elderly outpatients with diabetes and advanced chronic kidney disease

Contact Info

Product

Resources

About