Efficacy and safety of the glucagon receptor antagonist PF-06291874: A 12-week, randomized, dose-response study in patients with type 2 diabetes mellitus on background metformin therapy.
Diabetes Obes Metab
; 20(11): 2608-2616, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-29923286
ABSTRACT
AIMS:
To conduct a dose-response assessment of the efficacy and safety of the glucagon receptor antagonist PF-06291874 in adults with type 2 diabetes (T2DM) using stable doses of metformin. MATERIALS ANDMETHODS:
This randomized, double-blind, statin-stratified, placebo-controlled, 4-arm, parallel-group study was conducted in patients with T2DM who were receiving background metformin. After an 8-week, non-metformin oral antidiabetic agent washout period, 206 patients were randomized to placebo or PF-06291874 (30, 60 or 100 mg once daily) for 12 weeks. Glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG) and safety endpoints were assessed at baseline and post baseline.RESULTS:
Dose-dependent mean reductions from baseline in HbA1c for PF-06291874 ranged from -0.67% (-7.29 mmol/mol) to -0.93% (-10.13 mmol/mol), and for FPG from -16.6 to -33.3 mg/dL after 12 weeks of dosing. The incidence of hypoglycaemia was low and was similar between groups receiving PF-06291874 and placebo. Small, non-dose-dependent increases in LDL cholesterol (<10%) and blood pressure (BP) (systolic BP > 2 mm Hg; diastolic BP > 1 mm Hg) were observed with PF-06291874. Modest non-dose-dependent median increases were observed across PF-06291874 groups at 12 weeks for alanine aminotransferase (range, 37.6-48.7 U/L vs placebo) and aspartate aminotransferase (range, 33.3-36.6 U/L vs placebo); these were not associated with bilirubin changes. Small increases were observed in body weight (< 0.5 kg) in each PF-06291874 group vs placebo.CONCLUSIONS:
In patients with T2DM, PF-06291874 significantly lowered HbA1c and glucose, was well tolerated and carried a low risk of hypoglycaemia. Small, non-dose-related increases in BP, lipids and hepatic transaminases were observed.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Beta-Alanina
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Diabetes Mellitus Tipo 2
/
Metformina
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Diabetes Obes Metab
Ano de publicação:
2018
Tipo de documento:
Article