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Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

Kothny W, Lukashevich V, Foley JE, Rendell MS, Schweizer A - Diabetologia (2015)

Bottom Line: These doses are recommended in this patient population and considered maximally effective.Both treatments were well tolerated with overall similar safety profiles.At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Novartis Pharma AG, Postfach, CH-4002, Basel, Switzerland, wolfgang.kothny@novartis.com.

ABSTRACT

Aims/hypothesis: There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI).

Methods: This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR <30 ml min(-1) [1.73 m](-2) were randomised (via interactive voice response technology) to vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events.

Results: In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles.

Conclusions/interpretation: At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI.

Trial registration: ClinicalTrials.gov NCT00616811 (completed)

Funding: This study was planned and conducted by Novartis.

No MeSH data available.


Related in: MedlinePlus

(a) Adjusted mean (SE) change in HbA1c from baseline with vildagliptin 50 mg once daily (n = 78) or sitagliptin 25 mg once daily (n = 62), p = 0.874. (b) Adjusted mean (SE) change in FPG from baseline with vildagliptin 50 mg once daily (n = 79) or sitagliptin 25 mg once daily (n = 62), p = 0.185. (c) Percentage of patients achieving HbA1c ≤6.5% and ≤7.0% with vildagliptin 50 mg once daily (n = 69) or sitagliptin 25 mg once daily n = 56), p = 0.050. Black bars, vildagliptin 50 mg once daily; white bars, sitagliptin 25 mg once daily. To convert values for HbA1c in DCCT % into mmol/mol, subtract 2.15 and multiply by 10.929
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Fig2: (a) Adjusted mean (SE) change in HbA1c from baseline with vildagliptin 50 mg once daily (n = 78) or sitagliptin 25 mg once daily (n = 62), p = 0.874. (b) Adjusted mean (SE) change in FPG from baseline with vildagliptin 50 mg once daily (n = 79) or sitagliptin 25 mg once daily (n = 62), p = 0.185. (c) Percentage of patients achieving HbA1c ≤6.5% and ≤7.0% with vildagliptin 50 mg once daily (n = 69) or sitagliptin 25 mg once daily n = 56), p = 0.050. Black bars, vildagliptin 50 mg once daily; white bars, sitagliptin 25 mg once daily. To convert values for HbA1c in DCCT % into mmol/mol, subtract 2.15 and multiply by 10.929

Mentions: The adjusted mean changes in HbA1c and FPG during the 24 week treatment period as well as the percentage of patients achieving a target HbA1c ≤6.5% (48 mmol/mol) are represented in Fig. 2. The adjusted mean change in HbA1c was −0.54% ± 0.12% (5.9 ± 1.3 mmol/mol) from a baseline of 7.52% (59 mmol/mol) in the vildagliptin group and −0.56% ± 0.13% (6.1 ± 1.4 mmol/mol) from a baseline of 7.80% (62 mmol/mol) in the sitagliptin group (p = 0.874 for between-group difference; Fig. 2a). A reduction in FPG of 0.47 ± 0.37 mmol/l was seen with vildagliptin, while a slight increase of 0.16 ± 0.43 mmol/l was found with sitagliptin. This difference did not reach statistical significance given the relatively small cohorts (p = 0.185 for between-group difference; Fig. 2b). The percentage of patients achieving a target HbA1c ≤7.0% (53 mmol/mol) was similar in both treatment groups (39% vs 40%); however, the proportion of patients achieving a target HbA1c ≤6.5% (48 mmol/mol) in the vildagliptin group was twice that in the sitagliptin group (29.0% vs 14.3%; p = 0.050; Fig. 2c). Even though there was a trend towards lower FPG levels in the vildagliptin group, the incidence of hypoglycaemia was similar between the two treatment groups (16% vs 15%). Furthermore, as depicted in Table 2, several AEs probably related to hypoglycaemia were reported less frequently in the vildagliptin group than the sitagliptin group (33% vs 51%). This difference was primarily driven by AEs of hyperhidrosis, tremor and asthaenia, as well as asymptomatic low blood glucose levels.Fig. 2


Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

Kothny W, Lukashevich V, Foley JE, Rendell MS, Schweizer A - Diabetologia (2015)

(a) Adjusted mean (SE) change in HbA1c from baseline with vildagliptin 50 mg once daily (n = 78) or sitagliptin 25 mg once daily (n = 62), p = 0.874. (b) Adjusted mean (SE) change in FPG from baseline with vildagliptin 50 mg once daily (n = 79) or sitagliptin 25 mg once daily (n = 62), p = 0.185. (c) Percentage of patients achieving HbA1c ≤6.5% and ≤7.0% with vildagliptin 50 mg once daily (n = 69) or sitagliptin 25 mg once daily n = 56), p = 0.050. Black bars, vildagliptin 50 mg once daily; white bars, sitagliptin 25 mg once daily. To convert values for HbA1c in DCCT % into mmol/mol, subtract 2.15 and multiply by 10.929
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: (a) Adjusted mean (SE) change in HbA1c from baseline with vildagliptin 50 mg once daily (n = 78) or sitagliptin 25 mg once daily (n = 62), p = 0.874. (b) Adjusted mean (SE) change in FPG from baseline with vildagliptin 50 mg once daily (n = 79) or sitagliptin 25 mg once daily (n = 62), p = 0.185. (c) Percentage of patients achieving HbA1c ≤6.5% and ≤7.0% with vildagliptin 50 mg once daily (n = 69) or sitagliptin 25 mg once daily n = 56), p = 0.050. Black bars, vildagliptin 50 mg once daily; white bars, sitagliptin 25 mg once daily. To convert values for HbA1c in DCCT % into mmol/mol, subtract 2.15 and multiply by 10.929
Mentions: The adjusted mean changes in HbA1c and FPG during the 24 week treatment period as well as the percentage of patients achieving a target HbA1c ≤6.5% (48 mmol/mol) are represented in Fig. 2. The adjusted mean change in HbA1c was −0.54% ± 0.12% (5.9 ± 1.3 mmol/mol) from a baseline of 7.52% (59 mmol/mol) in the vildagliptin group and −0.56% ± 0.13% (6.1 ± 1.4 mmol/mol) from a baseline of 7.80% (62 mmol/mol) in the sitagliptin group (p = 0.874 for between-group difference; Fig. 2a). A reduction in FPG of 0.47 ± 0.37 mmol/l was seen with vildagliptin, while a slight increase of 0.16 ± 0.43 mmol/l was found with sitagliptin. This difference did not reach statistical significance given the relatively small cohorts (p = 0.185 for between-group difference; Fig. 2b). The percentage of patients achieving a target HbA1c ≤7.0% (53 mmol/mol) was similar in both treatment groups (39% vs 40%); however, the proportion of patients achieving a target HbA1c ≤6.5% (48 mmol/mol) in the vildagliptin group was twice that in the sitagliptin group (29.0% vs 14.3%; p = 0.050; Fig. 2c). Even though there was a trend towards lower FPG levels in the vildagliptin group, the incidence of hypoglycaemia was similar between the two treatment groups (16% vs 15%). Furthermore, as depicted in Table 2, several AEs probably related to hypoglycaemia were reported less frequently in the vildagliptin group than the sitagliptin group (33% vs 51%). This difference was primarily driven by AEs of hyperhidrosis, tremor and asthaenia, as well as asymptomatic low blood glucose levels.Fig. 2

Bottom Line: These doses are recommended in this patient population and considered maximally effective.Both treatments were well tolerated with overall similar safety profiles.At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Novartis Pharma AG, Postfach, CH-4002, Basel, Switzerland, wolfgang.kothny@novartis.com.

ABSTRACT

Aims/hypothesis: There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI).

Methods: This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR <30 ml min(-1) [1.73 m](-2) were randomised (via interactive voice response technology) to vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events.

Results: In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles.

Conclusions/interpretation: At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI.

Trial registration: ClinicalTrials.gov NCT00616811 (completed)

Funding: This study was planned and conducted by Novartis.

No MeSH data available.


Related in: MedlinePlus