Efficacy and Safety of Sitagliptin Versus Glipizide in Patients With Type 2 Diabetes and Moderate-to-Severe Chronic Renal Insufficiency

Ferreira, Juan Camilo Arjona; Marre, Michel; Barzilai, Nir; Guo, Hua; Golm, Gregory T.; Sisk, Christine Mc Crary; Kaufman, Keith D.; Goldstein, Barry J.

doi:10.2337/dc12-1365

Cited by 132 publications

(86 citation statements)

References 20 publications

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“…Glipizide (2.5 mg once daily, adjusted based on glycemic control to a 10-mg twice a day maximum dose) was evaluated in patients with T2DM and moderate-to-severe CKD and inadequate glycemic control. A higher incidence of symptomatic hypoglycemic episodes was observed with glipizide versus sitagliptin (17.0% versus 6.2%, respectively; P=0.001), for a comparable glucose-lowering efficacy, an observation similar to that previously reported in patients without RI 74 . Similar results were obtained in a recent study that compared the efficacy and safety of sitagliptin and glipizide monotherapy in patients with T2DM and ESRD on dialysis therapy 75 .…”

Section: Glipizidesupporting

confidence: 84%

“…Sitagliptin was generally well-tolerated, with a lower risk of hypoglycemia and weight loss versus weight gain, relative to glipizide 74 . In patients with T2DM and ESRD on dialysis therapy, sitagliptin 25 mg/day was almost as effective in reducing HbA1c as glipizide (non significant difference of 0.15% after 54 weeks), with a lower incidence of symptomatic hypoglycemia (6.3 % vs.…”

Section: Sitagliptinmentioning

confidence: 97%

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Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Scheen¹

2013

Expert Opinion on Drug Metabolism & Toxicology

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SUMMARYIntroduction : People with chronic kidney disease (CKD) of stages 3-5 (creatinine clearance < 60 ml/min) represent 25-30% of patients with type 2 diabetes (T2DM), but the problem is underrecognized or neglected in clinical practice. However, most oral antidiabetic agents have limitations in case of renal impairment, either because they require a dose adjustment or because they are contraindicated for safety reasons. Expert Opinion : Because of potential important PK interferences and for safety reasons, the pharmacological management of T2DM should be adjusted according to kidney function. In general, the daily dose should be reduced according to glomerular filtration rate (GFR) or even the drug is contraindicated in presence of more severe CKD. This is the case for metformin (risk of lactic acidosis) and for many sulfonylureas (risk of hypoglycemia). At present, however, the exact GFR cutoff for metformin use is controversial. New antidiabetic agents are better tolerated in case of CKD, although clinical experience remains quite limited for most of them. The dose of DPP-4 inhibitors should be reduced (except for linaglitpin) whereas both the efficacy and safety of SGLT2 inhibitors are questionable in presence of CKD.

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Section: Glipizidesupporting

confidence: 84%

Section: Sitagliptinmentioning

confidence: 97%

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Scheen¹

2013

Expert Opinion on Drug Metabolism & Toxicology

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“…The pooling excluded studies conducted in patients with moderate-to-severe renal insufficiency, because these patients received sitagliptin at doses less than 100 mg/day. Studies describing the safety and tolerability of sitagliptin in patients with moderate and severe renal insufficiency have been previously published [7–9]. …”

Section: Methodsmentioning

confidence: 99%

Safety and Tolerability of Sitagliptin in Type 2 Diabetes: Pooled Analysis of 25 Clinical Studies

et al. 2013

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IntroductionIn a previous pooled analysis of 19 double-blind clinical studies conducted by Merck, which included data available as of July 2009 on 10,246 patients with type 2 diabetes (T2DM), treatment with sitagliptin was shown to be generally well tolerated compared with treatment with control agents. As the sitagliptin clinical development program continues, additional studies with sitagliptin have been completed. The present analysis updates the safety and tolerability assessment of sitagliptin by examining pooled data from 25 double-blind clinical studies.MethodsThe present analysis included data from 14,611 patients in 25 studies with T2DM who received either sitagliptin 100 mg/day (n = 7,726; sitagliptin group) or a comparator agent (n = 6,885; non-exposed group). These studies represent all randomized, double-blind trials conducted by Merck that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years, and for which results were available as of December 2011. These studies assessed sitagliptin, versus comparator agents, taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or metformin + pioglitazone or rosiglitazone). Patient-level data from each study were used to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events (AEs).ResultsOverall incidence rates of AEs and drug-related AEs were higher in the non-exposed group compared with the sitagliptin group. Incidence rates of specific AEs were generally similar between the two groups, except for higher incidence rates of hypoglycemia related to the greater use of a sulfonylurea and diarrhea related to the greater use of metformin in the non-exposed group, and of constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events, malignancy, or pancreatitis.ConclusionIn this updated pooled safety analysis of data from 14,611 patients with T2DM, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration.

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“…Two studies compared DPP-4 inhibitor monotherapy with glipizide monotherapy [24]–[25]. In addition, two studies used placebo as a control for the first period (12 weeks) followed by an extended 40–42-week sulfonylurea treatment, which was ignored because of the potential influence of the first period [16], [23].…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Mellitus Patients with Moderate to Severe Renal Impairment: A Systematic Review and Meta-Analysis

et al. 2014

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ObjectiveTo perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors (“gliptins”) for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment.MethodsAll available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials.gov, pharmaceutical company websites, the FDA, and the EMA (up to June 2014). Two independent reviewers extracted the data, and a random-effects model was applied to estimate summary effects.ResultsThirteen reports of ten studies with a total of 1,915 participants were included in the final analysis. Compared with placebo or no treatment, DPP-4 inhibitors reduced HbA1c significantly (−0.52%, 95%CI −0.64 to −0.39) and had no increased risk of hypoglycemia (RR 1.10, 95%CI 0.92 to 1.32) or weight gain. In contrast to glipizide monotherapy, DPP-4 inhibitors showed no difference in HbA1c lowering effect (−0.08%, 95% CI −0.40 to 0.25) but had a lower incidence of hypoglycemia (RR 0.40, 95%CI 0.23 to 0.69). Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events. However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.ConclusionsDPP-4 inhibitors are effective at lowering HbA1c in T2DM patients with moderate to severe renal impairment. DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events. Regarding the low quality of the evidence according to GRADE, additional well-designed randomized trials that focus on the safety and efficacy of DPP-4 inhibitors in various CKD stages are needed urgently.

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Efficacy and Safety of Sitagliptin Versus Glipizide in Patients With Type 2 Diabetes and Moderate-to-Severe Chronic Renal Insufficiency

Cited by 132 publications

References 20 publications

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Safety and Tolerability of Sitagliptin in Type 2 Diabetes: Pooled Analysis of 25 Clinical Studies

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Mellitus Patients with Moderate to Severe Renal Impairment: A Systematic Review and Meta-Analysis

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