The effect of alogliptin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy.
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SUBMITTER: Tai H
PROVIDER: S-EPMC5370803 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
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The effect of alogliptin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy.
Tai He H Wang Ming-Yue MY Zhao Yue-Ping YP Li Ling-Bing LB Dong Qian-Yan QY Liu Xin-Guang XG Kuang Jin-Song JS
Medicine 20160801 33
<h4>Background</h4>To observe the effect of alogliptin combined with metformin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy (500 mg, bid po, for at least 3 months), and evaluate its efficacy and safety.<h4>Methods</h4>After a 2-week screening period, adult patients (aged 36-72 years) entered a 4-week run-in/stabilization period. Then, patients were randomly assigned to either the intervention group (n = 55) or the control group (n ...[more]
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Project description:BackgroundThis study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy.MethodsFifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-β, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index).ResultsAt baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p < 0.001), and from 8.2 ± 0.8% to 7.5 ± 0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly increased from 51.2 ± 24.2 to 74.9 ± 41.9 (p < 0.05), and in the acarbose group, from 62.5 ± 31.4 to 91.7 ± 36.2 (p < 0.05), respectively. Multiple regression analyses showed that both baseline HbA1c and DI120 independently predicted reduction of HbA1c as well as final HbA1c after combination therapy.ConclusionsIn patients with T2DM inadequately controlled with metformin, add-on oral anti-diabetic agent with glibenclamide or acarbose resulted in the significant HbA1c reduction and improvement of β-cell function. Subjects with greater baseline β-cell function reserve displayed better glycemic response in the combination therapy of metformin with glibenclamide or acarbose.Trial registrationThis study was registered in the ClinicalTrials.gov with registration number of NCT00417729.
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Project description:AimTo evaluate the long-term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin.Materials and methodsA 104-week Phase III, randomized double-blind study with a 26-week placebo-controlled period (Phase A) and a 78-week period (Phase B) where blinded glimepiride was added to non-rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported.ResultsMean (standard error) change in HbA1c from baseline was -0.7% (0.07) and -1.0% (0.07) at week 52; -0.6% (0.08) and -0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) -0.50% (-0.95, -0.04) at week 52 and -0.84% (-1.44, -0.24) at week 104.ConclusionsErtugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non-clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: NCT02033889.
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| S-EPMC3087768 | biostudies-literature
Project description:ObjectiveTo determine if the dipeptidyl peptidase-4 inhibitor vildagliptin more effectively inhibits glucagon levels than the sulfonylurea glimepiride during a meal.Research design and methodsGlucagon responses to a standard meal were measured at baseline and study end point (mean 1.8 years) in a trial evaluating add-on therapy to metformin with 50 mg vildagliptin b.i.d. compared with glimepiride up to 6 mg q.d. in type 2 diabetes (baseline A1C 7.3 +/- 0.6%).ResultsA1C and prandial glucose area under the curve (AUC)(0-2 h) were reduced similarly in both groups, whereas prandial insulin AUC(0-2 h) increased to a greater extent by glimepiride. Prandial glucagon AUC(0-2 h) (baseline 66.6 +/- 2.3 pmol . h(-1) . l(-1)) decreased by 3.4 +/- 1.6 pmol . h(-1) . l(-1) by vildagliptin (n = 137) and increased by 3.8 +/- 1.7 pmol . h(-1) . l(-1) by glimepiride (n = 121). The between-group difference was 7.3 +/- 2.1 pmol . h(-1) . l(-1) (P < 0.001).ConclusionsVildagliptin therapy but not glimepiride improves postprandial alpha-cell function, which persists for at least 2 years.
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Project description:AimsTo demonstrate the noninferiority of alogliptin to acarbose, in terms of antidiabetic efficacy, in Chinese people with uncontrolled type 2 diabetes (T2D) and high cardiovascular risk.Materials and methodsACADEMIC (NCT03794336) was a randomized, open-label, phase IV study conducted at 46 sites in China. Antidiabetic treatment-naive or metformin-treated adults with uncontrolled T2D (glycated haemoglobin [HbA1c] 58.0-97.0 mmol/mol) were randomized 2:1 to alogliptin 25 mg once daily or acarbose 100 mg three times daily for 16 weeks. All participants had a documented history of coronary heart disease or high cardiovascular risk at screening and received aspirin (acetylsalicylic acid) 100 mg daily throughout the trial. The primary endpoints were change in HbA1c versus baseline, and the incidence of gastrointestinal adverse events (AEs). Safety and tolerability were also assessed.ResultsA total of 1088 participants were randomized. Alogliptin was noninferior to acarbose for the change in Week-16 HbA1c (least-squares mean change [standard error] -11.9 [0.4] vs. -11.4 [0.5] mmol/mol, respectively; difference between arms -0.5 [0.7] mmol/mol; 95% confidence interval -1.9 to 0.8 mmol/mol), and was associated with a lower incidence of gastrointestinal AEs (8.9% vs. 33.6%, respectively; P < 0.0001). More alogliptin than acarbose recipients achieved HbA1c <53.0 mmol/mol without gastrointestinal AEs (48.0% vs. 32.7%; P < 0.0001). Discontinuations due to treatment-related AEs were less frequent with alogliptin than acarbose (0.3% vs. 2.5%).ConclusionsGlycaemic control was comparable between alogliptin and acarbose, but the gastrointestinal tolerability of alogliptin was better. More patients achieved target HbA1c without gastrointestinal AEs with alogliptin, suggesting that this agent may be preferred in clinical practice.
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Project description:BackgroundManagement of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.MethodsThis was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.ResultsA total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg).ConclusionsDapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone.Trial registrationClinicalTrials.gov: NCT00528879.
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