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: 6.36). 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.

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    • "Against this background our results are somewhat surprising especially in comparison to analyses predicting anamnestic hypoglycaemia in DiaRegis but have to be weighed against a number of changes that were introduced over the course of 12 months: 1) sulfonylurea use was reduced between baseline and the 12 months follow-up from 29.5 to 24.2%, at least partially also because of hypoglycaemia; 2) oral monotherapy went down from 68.4% at baseline to 17.8% at the 1 year FU in favour of combined OAD treatment regimens and insulin / GLP-1 analogue use. This may have masked hypoglycaemia rates seen with sulfonylureas as has been shown to be the case in combination with for example DPP-4 inhibitors [26,27]. Finally rates of hypoglycaemia were lower for anamnestic or recalled episodes than those prospectively collected in the patient's diary. "
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    ABSTRACT: Aims: With the intensification of antidiabetic treatment, there is an increasing risk of hypoglycaemia. We aimed to determine incidence, characteristics and outcomes. Methods: Prospective, observational, multicenter cohort study. The included 3810 patients with type 2 diabetes had their treatment intensified at baseline. Results: The incidence of hypoglycaemia was 11.4% per year with 4.2 ± 4.4 episodes per patient. Hypoglycaemia was more frequent in patients with high blood glucose variability. Predictors were heart failure (odds ratio: 1.66; 95% confidence interval: 1.20-2.29) and insulin use (odds ratio: 4.03; 95% confidence interval: 3.05-5.33), with dipeptidyl peptidase-4 inhibitors being associated with reduced risk (odds ratio: 0.69; 95% confidence interval: 0.53-0.89). Macrovascular events were more frequent among patients reporting severe episodes of hypoglycaemia (odds ratio: 3.39; 95% confidence interval: 1.32-8.73). Microvascular events were more frequent in patients with non-severe episodes (odds ratio: 1.92; 95% confidence interval: 1.49-2.49). Conclusion: Case-by-case evaluation of patients as well as appropriate selection of antidiabetic pharmacotherapy and blood glucose treatment goals could maximize the benefits while reducing the risks of antidiabetic treatment.
    No preview · Article · Nov 2015 · Diabetes & Vascular Disease Research
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    • "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. "
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    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.
    Full-text · Article · Jul 2015 · SpringerPlus
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    • "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.
    Full-text · Article · Jul 2015 · SpringerPlus
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