Article

Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: A randomized, double-blind, non-inferiority trial

Diabeteszentrum Bad Lauterberg im Harz, Bad Lauterberg, Germany.
Diabetes Obesity and Metabolism (Impact Factor: 5.46). 04/2007; 9(2):194-205. DOI: 10.1111/j.1463-1326.2006.00704.x
Source: PubMed

ABSTRACT To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A(1c) (HbA(1c)) > or = 6.5 and < or = 10%] on metformin monotherapy.
After a metformin dose titration/stabilization period (> or = 1500 mg/day), 1172 patients were randomized to the addition of sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (uptitrated to a potential maximum 20 mg/day) (N = 584) for 52 weeks. The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA(1c) changes from baseline at Week 52 using a per-protocol approach.
From a mean baseline of 7.5%, HbA(1c) changes from baseline were -0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA(1c) < 7% were 63% (sitagliptin) and 59% (glipizide). Fasting plasma glucose changes from baseline were -0.56 mmol/l (-10.0 mg/dl) and -0.42 mmol/l (-7.5 mg/dl) for sitagliptin and glipizide, respectively. The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0.001) higher with glipizide (32%) than with sitagliptin (5%), with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients. Sitagliptin led to weight loss (change from baseline =-1.5 kg) compared with weight gain (+1.1 kg) with glipizide [between-treatment difference (95% confidence interval) =-2.5 kg (-3.1, -2.0); p < 0.001].
In this study, the addition of sitagliptin compared with glipizide provided similar HbA(1c)-lowering efficacy over 52 weeks in patients on ongoing metformin therapy. Sitagliptin was generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide.

Download full-text

Full-text

Available from: Gary Meininger, Apr 08, 2015
0 Followers
 · 
312 Views
  • Source
    • "As stated above, DM is closely related to chronic liver injury. On the other hand, since most oral hypoglycemic agents are metabolized in the liver and may induce liver damage, the treatment of T2DM patients with chronic liver injury is often difficult (Nauck et al. 2007). Since the DPP-4 inhibitor sitagliptin is minimally metabolized in the liver and over 80% is excreted in an unaltered state in the urine (Drucker and Nauck 2006), it is expected that the pharmacokinetic of sitagliptin will have few negative effects even in patients with chronic liver injury. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To investigate the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, sitagliptin, for treating diabetes mel-litus complicated by chronic liver injury. Methods: Sitagliptin was administered for 13.7 ± 10.1 months to 122 patients with DM complicated by chronic liver injury (including 19 patients with liver cirrhosis), and changes in hemoglobin A1c (HbA1c) and liver enzymes (transaminases, etc.) were evaluated. Results: HbA1c was reduced from 8.48 ± 1.43% to 7.87 ± 1.35% (P < 0.001). Among liver enzymes, alanine ami-notransferase (ALT) levels improved from 75.1 ± 45.2 to 65.8 ± 35.8 IU/L (P = 0.012) and gamma-glut amyl-trans peptidase from 155.2 ± 161.1 to 133.2 ± 127.4 IU/L (P = 0.044). Among the causes of liver injury, non-alcoholic fatty liver disease and alcoholic liver disease both showed the reductions in HbA1c with no deterioration of liver enzymes. An analysis of 19 patients with liver cirrhosis also showed reductions in HbA1c with no deterioration of liver enzymes. Conclusion: It is suggested that sitagliptin can be administered effectively and safely to patients with diabetes mel-litus complicated by chronic liver injury, including liver cirrhosis.
    SpringerPlus 07/2015; 4.
  • Source
    • "As stated above, DM is closely related to chronic liver injury. On the other hand, since most oral hypoglycemic agents are metabolized in the liver and may induce liver damage, the treatment of T2DM patients with chronic liver injury is often difficult (Nauck et al. 2007). Since the DPP-4 inhibitor sitagliptin is minimally metabolized in the liver and over 80% is excreted in an unaltered state in the urine (Drucker and Nauck 2006), it is expected that the pharmacokinetic of sitagliptin will have few negative effects even in patients with chronic liver injury. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, sitagliptin, for treating diabetes mellitus complicated by chronic liver injury. Sitagliptin was administered for 13.7 ± 10.1 months to 122 patients with DM complicated by chronic liver injury (including 19 patients with liver cirrhosis), and changes in hemoglobin A1c (HbA1c) and liver enzymes (transaminases, etc.) were evaluated. HbA1c was reduced from 8.48 ± 1.43% to 7.87 ± 1.35% (P < 0.001). Among liver enzymes, alanine aminotransferase (ALT) levels improved from 75.1 ± 45.2 to 65.8 ± 35.8 IU/L (P = 0.012) and gamma-glut amyl-trans peptidase from 155.2 ± 161.1 to 133.2 ± 127.4 IU/L (P = 0.044). Among the causes of liver injury, non-alcoholic fatty liver disease and alcoholic liver disease both showed the reductions in HbA1c with no deterioration of liver enzymes. An analysis of 19 patients with liver cirrhosis also showed reductions in HbA1c with no deterioration of liver enzymes. It is suggested that sitagliptin can be administered effectively and safely to patients with diabetes mellitus complicated by chronic liver injury, including liver cirrhosis.
    SpringerPlus 01/2015; 4:346. DOI:10.1186/s40064-015-1135-z
  • Source
    • "En revanche, sous ces différentes bithérapies (avec la metformine) le nombre d'épisodes hypoglycémiques était très faible sous gliptines et analogues du GLP-1 (comme avec les IAG et les glitazones), quatre à cinq fois supérieurs sous sulfonylurées, sept fois plus élevé sous glinide (Novonorm W ). Cette différence marquée, pour le nombre total d'épisodes hypoglycémique enregistrés, est encore mieux illustrée par certaines études [17] [18]. Ainsi, la bithérapie metformine–vildagliptine (Galvus W ) vs glimépiride, pour une baisse similaire d'HbA1c (valeurs atteintes après 52 semaines de traitement : 6,72 et 6,75 %) il fut enregistré en nombre d'épisodes hypoglycémiques perçus 1,7 % sous vildagliptine vs 16,2 % sous glimépiride (39 vs 554), et surtout 11 patients du groupe glimépiride sont sortis d'étude en raison d'hypoglycémies sévères vs aucun du groupe vildagliptine [17]. Les données sont similaires avec la sitagliptine. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Once lifestyle measures implemented, if hyperglycemia persists, above individual HbA1c targets, a medication should be started in type 2 diabetic patients (T2DM). First, unless exception, an oral antidiabetic drug. Except in case of intolerance, the initial monotherapy, metformin remains the strengthening treatment. Latter, combination of two oral drugs, now offers several options, mainly the choice to associate a "conventional insulin-secretor", sulfonylureas, glinide, or a "new one" belonging the class of "incretin", more readily a gliptine (DPP-4 inhibitors) rather than injectable GLP-1 analogue which can also be sometimes chosen at this stage. These options are mostly new and have the advantage a neutral or favourable (for GLP-1) effect on body weight in obese type 2 DM patient and the absence of any hypoglycaemic risk in both classes of incretins. But this risk varies depending on the patient profile, much higher if the target HbA1c is low (6 to 6.5 or 7%), or in the elderly, fragile and/or in case of renal insufficiency. These two different situations with a high risk of hypoglycaemia, define best indications of this new class. If dual oral therapy does not achieve the goals we are faced with three options: triple oral therapy: metformin-sulfonylurea-gliptine or one of two approaches with injections, insulin or GLP-1 analogues. The use of GLP-1 analogues is often delayed today and put wrongly in balance with the transition to insulin, a use already delayed in France and insufficient. The use of incretins is new and needs to be validated by studies of sustainability on glycemic control, prevention of microvascular and macrovascular complications and after years on the market security of use, primarily on the exocrine pancreas. In short, individualization of strategies and HbA1c targets are required, the new molecules can help us in this process. This individualization can easily be done through the handy guide proposed by the experts ADA EASD statement, endorsed by the SFD, abandoning the complex algorithm recently again proposed by HAS and ANSM in 2013. A recommendation that prioritizes the costs of the strategies. An absolutely critical issue, while admitting not to have the tools to measure them in all their dimensions. Finally, we must reconsider every treatment after a maximum of 6months of use, if the results are deemed inadequate substitute rather than adding drugs.
    La Presse Médicale 05/2013; · 1.17 Impact Factor
Show more