Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

Abstract

Aim:

Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials.

Methods:

Safety data were pooled from 38 studies of ≥12 to ≥104 weeks’ duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths.

Results:

Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas.

Conclusions:

The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.

Keywords:

• type 2 diabetes
• dipeptidyl peptidase-4
• edema
• safety
• vildagliptin

Supplementary material

Table S1 Vildagliptin studies contributing to safety analyses

References

• RisticSByiersSFoleyJHolmesDImproved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose responseDiabetes Obes Metab2005769269816219012
   PubMed Web of Science ®Google Scholar
• PratleyREJauffret-KamelSGalbreathEHolmesDTwelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetesHorm Metab Res20063842342816823726
   PubMed Web of Science ®Google Scholar
• DejagerSRazacSFoleyJESchweizerAVildagliptin in drug-naive patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose studyHorm Metab Res20073921822317373638
   PubMed Web of Science ®Google Scholar
• ScherbaumWASchweizerAMariAEfficacy and tolerability of vildagliptin in drug-naive patients with type 2 diabetes and mild hyperglycemiaDiabetes Obes Metab20081067568218248490
   PubMed Web of Science ®Google Scholar
• MariAScherbaumWANilssonPMCharacterization of the influence of vildagliptin on model-assessed {beta}-cell function in patients with type 2 diabetes and mild hyperglycemiaJ Clin Endocrinol Metab20089310310917925336
   PubMed Web of Science ®Google Scholar
• ScherbaumWASchweizerAMariAEvidence that vildagliptin attenuates deterioration of glycaemic control during 2-year treatment of patients with type 2 diabetes and mild hyperglycaemiaDiabetes Obes Metab2008101114112418355325
   PubMed Web of Science ®Google Scholar
• SchweizerACouturierAFoleyJEDejagerSComparison between vildagliptin and metformin to sustain reductions in HbA1c over one year in drug-naïve patients with type 2 diabetesDiabet Med20072495596117509069
   PubMed Web of Science ®Google Scholar
• GökeBHershonKKerrDEfficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naive patients with type 2 diabetes: comparison with metforminHorm Metab Res20084089289518726829
   PubMed Web of Science ®Google Scholar
• FoleyJESreenanSEfficacy and safety comparison between the DPP-4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug-naive patients with type 2 diabetesHorm Metab Res20094190590919705345
   PubMed Web of Science ®Google Scholar
• PanCYangWBaronaJPComparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week, double-blind, randomized trialDiabet Med20082543544118341596
   PubMed Web of Science ®Google Scholar
• RosenstockJBaronMADejagerSComparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trialDiabetes Care20073021722317259484
   PubMed Web of Science ®Google Scholar
• RosenstockJNiggliMMaldonado-LutomirskyMLong-term 2-year safety and efficacy of vildagliptin compared with rosiglitazone in drug-naive patients with type 2 diabetes mellitusDiab Obes Metab200911571578
   PubMed Web of Science ®Google Scholar
• RosenstockJFoleyJERendellMEffects of the DPP-4 inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose toleranceDiabetes Care200831303517947341
   PubMed Web of Science ®Google Scholar
• Pi-SunyerFXSchweizerAMillsDDejagerSEfficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetesDiabetes Res Clin Pract20077613213817223217
   PubMed Web of Science ®Google Scholar
• SchweizerADejagerSBosiEComparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trialDiabetes Obes Metab20091180481219476473
   PubMed Web of Science ®Google Scholar
• AhrénBGomisRStandlETwelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetesDiabetes Care2004272874288015562200
   PubMed Web of Science ®Google Scholar
• BosiECamisascaRPColloberCEffects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metforminDiabetes Care20073089089317277036
   PubMed Web of Science ®Google Scholar
• FerranniniEFonsecaVZinmanBFifty-two-week efficacy and safety of vildagliptin vs glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapyDiabetes Obes Metab20091115716619125777
   PubMed Web of Science ®Google Scholar
• MatthewsDRDejagerSAhrenBVildagliptin add-on to metformin produces similar efficacy and reduced hypoglyceamic risk compared with glimepiride, with no weight gain: results from a 2-year studyDiabetes Obes Metab201012978078920649630
   PubMed Web of Science ®Google Scholar
• FilozofCGautierJFA comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone: a 52-week, randomized studyDiab Med 201;273318326
   PubMed Web of Science ®Google Scholar
• BolliGDottaFRochotteECohenSEEfficacy and tolerability of vildagliptin vs pioglitazone when added to metformin: a 24-week, randomized, double-blind studyDiabetes Obes Metab200810829018034842
   PubMed Web of Science ®Google Scholar
• BolliGDottaFColinLComparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metforminDiabetes Obes Metab20091158959519515179
   PubMed Web of Science ®Google Scholar
• GoodmanMThurstonHPenmanJEfficacy and tolerability of vildagliptin in patients with type 2 diabetes inadequately controlled with metformin monotherapyHorm Metab Res20094136837319221978
   PubMed Web of Science ®Google Scholar
• FilozofCSchwartzSFoleyJEEffect of metformin as add-on therapy to a low dose metforminWorld J Diabetes201011926
   PubMedGoogle Scholar
• BosiEDottaFJiaYGoodmanMVildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitusDiabetes Obes Metab20091150651519320662
   PubMed Web of Science ®Google Scholar
• GarberAJSchweizerABaronMAVildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled studyDiabetes Obes Metab2007916617417300592
   PubMed Web of Science ®Google Scholar
• RosenstockJBaronMACamisascaRPEfficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared to component monotherapy in patients with type 2 diabetesDiabetes Obes Metab2007917518517300593
   PubMed Web of Science ®Google Scholar
• GarberAJFoleyJEBanerjiMAEffects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylureaDiabetes Obes Metab2008101047105618284434
   PubMed Web of Science ®Google Scholar
• FonsecaVSchweizerAAlbrechtDAddition of vildagliptin to insulin improves glycaemic control in type 2 diabetesDiabetologia2007501148115517387446
   PubMed Web of Science ®Google Scholar
• FonsecaVBaronMShaoQDejagerSSustained efficacy and reduced hypoglycemia during one year of treatment with vildagliptin added to insulin in patients with type 2 diabetes mellitusHorm Metab Res20084042743018401832
   PubMed Web of Science ®Google Scholar

Acknowledgements

The authors acknowledge the patients, investigators, and staff at participating sites for all the studies. This work was funded by Novartis Pharmaceuticals Corporation.

Declaration

All authors are employees of Novartis.