Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Vascular Health and Risk Management 01/2013; 9(1):21-8. DOI: 10.2147/VHRM.S39300
Source: PubMed


The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m(2)) and longstanding type 2 diabetes not adequately controlled with insulin therapy, which is a difficult-to-treat population, with limited therapeutic options and a high susceptibility to hypoglycemia.
This was a post hoc subanalysis of data obtained during a previously described randomized, double-blind, parallel-group, 24-week study comparing the efficacy and safety of vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m(2), 100 randomized to vildagliptin, 78 randomized to placebo), all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent) for longstanding type 2 diabetes (mean approximately 19 years).
With vildagliptin in combination with insulin, the adjusted mean change (AMΔ) in HbA(1c) from baseline (7.7% ± 0.1%) was -0.9% ± 0.4% and the between-treatment difference (vildagliptin - placebo) was -0.6% ± 0.2% (P < 0.001). The percentage of patients achieving endpoint HbA(1c) < 7.0% was significantly higher with vildagliptin than placebo (45.2% versus 22.8%, P = 0.008). When added to insulin, vildagliptin and placebo had comparable hypoglycemic profiles and did not cause weight gain. Both treatments were similarly well tolerated, with comparable incidences of adverse events, serious adverse events, and deaths.
When added to insulin therapy in patients with severe renal impairment and longstanding type 2 diabetes, vildagliptin 50 mg once daily was efficacious, eliciting HbA(1c) reductions consistent with those previously reported for a patient population with much more recent onset of type 2 diabetes and normal renal function, and had a hypoglycemic profile comparable with placebo. Accordingly, vildagliptin is a suitable treatment option for patients with advanced type 2 diabetes and impaired renal function who require insulin therapy and present a serious therapeutic challenge in clinical practice.

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Available from: James E Foley, May 19, 2014
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    • "The magnitude of the glucose-lowering seen in this subgroup (HbA1c reduction of −1.0% from a baseline of 7.8%) was similar to that seen previously in patients ≥75 years with mostly normal renal function or mild RI receiving vildagliptin monotherapy or add-on therapy to metformin (−0.9% to −1.1%) [16] or in a population with severe RI with a mean age of 64 years receiving background insulin therapy (−0.9%) [18], which was also reported to be consistent with that seen for vildagliptin in the general population in monotherapy or combination therapy studies. Relative to placebo, the decrease in HbA1c (−0.8%) was clinically meaningful, with more than half of the vildagliptin-treated patients reaching an HbA1c ≤7.5%, regarded an appropriate target for this patient population [3, 21, 22]. "
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    ABSTRACT: Patients with type 2 diabetes (T2DM) are at increased risk for renal impairment (RI) and, in addition, there is an age-related decline in renal function. At the same time, T2DM treatment is more complex and treatment options are more limited in elderly patients as well as patients with RI, with the patient population ≥75 years with moderate or severe RI posing unique challenges, in particular, the high risk and more severe consequences of hypoglycemia. It was, therefore, of interest to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor vildagliptin in patients with T2DM ≥75 years who also have moderate or severe RI. In this sub-analysis of data derived from a previously described randomized, double-blind, parallel-group, 24-week study, 105 patients (50 randomized to vildagliptin 50 mg qd and 55 to placebo) ≥75 years (mean age ~78 years) with T2DM and moderate or severe RI (mean baseline estimated glomerular filtration rate ~35 ml/min/1.73 m(2)) were included. The adjusted mean change in glycated hemoglobin (HbA1c) with vildagliptin was -1.0% from a baseline of 7.8% (between-group difference -0.8%; p < 0.001). This improvement in glycemic control was not associated with an increased risk of hypoglycemia; the rate of confirmed hypoglycemia was 0.49 events per patient-year with vildagliptin and 0.96 events per patient-year with placebo (not significant). Weight remained stable with vildagliptin treatment. Adverse events (AEs) (58.0% vs. 72.7%), serious AEs (14.0% vs. 16.4%), discontinuations due to AEs (4.0% vs. 9.1%) and deaths (0% vs. 5.5%) were reported at a comparable or lower frequency in patients receiving vildagliptin versus patients receiving placebo. In this uniquely fragile elderly population ≥75 years with T2DM and moderate or severe RI, vildagliptin was well tolerated and efficacious, with no increase in the rate of hypoglycemia compared to placebo despite the marked improvement in glycemic control.
    07/2013; 4(2). DOI:10.1007/s13300-013-0027-x
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    • "Vildagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, is a novel OHA that can be used in patients with type 2 diabetes mellitus and renal impairment [8–10]. However, few reports have investigated the clinical effectiveness of vildagliptin in diabetic patients undergoing hemodialysis [11, 12]. "
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    ABSTRACT: Vildagliptin can be used in patients with type 2 diabetes mellitus and renal impairment. However, there have been few reports investigating the clinical effectiveness of vildagliptin in diabetic patients undergoing hemodialysis. No previous studies have evaluated the use of vildagliptin in patients undergoing peritoneal dialysis. The authors determined the usefulness of vildagliptin for treating type 2 diabetic patients receiving chronic dialysis, including peritoneal dialysis. A retrospective study of ten diabetic patients undergoing peritoneal dialysis and five diabetic patients undergoing hemodialysis who were treated with 50 mg/day of vildagliptin was performed. Clinical parameters were investigated for a period of 6 months starting from the vildagliptin therapy. The hemoglobin A1c (HbA1c) levels were significantly reduced after baseline in both the peritoneal dialysis and hemodialysis groups, whereas the hemoglobin levels did not change during the follow-up period. The mean change in the HbA1c level (ΔHbA1c) was -0.6 ± 0.9% and -0.5 ± 0.7% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. The glycated albumin (GA) levels were also significantly reduced compared with baseline in the peritoneal dialysis group, although the serum albumin levels did not change. The mean change in the GA level (ΔGA) was -3.4 ± 3.1% and -2.1 ± 2.5% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. Stepwise multivariate analyses demonstrated the level of HbA1c at baseline to be significantly associated with the ΔHbA1c and that the level of GA at baseline was significantly associated with the ΔGA. Vildagliptin exhibits effectiveness in patients with type 2 diabetes mellitus undergoing peritoneal dialysis or hemodialysis. The degree of improvement in the HbA1c and GA levels was dependent on these levels at baseline, similar to the findings of previous reports of subjects without end-stage kidney disease.
    06/2013; 4(2). DOI:10.1007/s13300-013-0029-8
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    • "In a recent 24-week study of vildagliptin (50 mg once daily [qd]) in 515 patients with moderate or severe RI,23 the vast majority of patients with severe RI (~80%; n = 178; estimated glomerular filtration rate [eGFR] ~21 mL/min/1.73 m2) were receiving insulin background therapy, which allowed a subanalysis to be performed to evaluate vildagliptin in combination with insulin in this difficult to treat patient population.24 Patients had a mean duration of T2DM of ~19 years and had received insulin therapy for an average of ~5 years. "
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    ABSTRACT: Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with vildagliptin, metformin, and basal insulin could be an attractive therapeutic option.
    Vascular Health and Risk Management 02/2013; 9(1):57-64. DOI:10.2147/VHRM.S40972
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