PMID- 18355324 OWN - NLM STAT- MEDLINE DCOM- 20080804 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 10 IP - 5 DP - 2008 May TI - Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. PG - 376-86 LID - 10.1111/j.1463-1326.2008.00876.x [doi] AB - AIM: Enhancing the physiologic actions of the endogenous incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, by inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for their degradation, is an emerging treatment for type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the safety and efficacy of dose ranges of the DPP-4 inhibitor saxagliptin (BMS-477118) in patients with T2DM. METHODS: In a 12-week, multicentre, randomized, parallel-group, double-blind, placebo-controlled trial conducted at 152 out-patient US study centres, 338 (low-dose cohort) and 85 (high-dose cohort) drug-naive patients with T2DM and inadequate glycaemic control (baseline HbA1c > or =6.8 and < or =9.7%) were randomized. Following a 2-week washout, patients received saxagliptin 2.5, 5, 10, 20 or 40 mg once daily, or placebo, for 12 weeks (low-dose cohort). In a second cohort, patients received saxagliptin 100 mg once daily, or placebo, for 6 weeks (high-dose cohort). The main outcome measure was saxagliptin dose response assessed as change from baseline in HbA1c following double-blind treatment. RESULTS: In all treatment arms, saxagliptin significantly reduced HbA1c by 0.7-0.9% from an average baseline of 7.9% vs. placebo (0.3% reduction) in the low-dose cohort. Placebo-subtracted HbA1c reductions were 0.45-0.63% (low-dose cohort). Saxagliptin had significant placebo-subtracted reductions in fasting serum glucose (14-25 mg/dl). Postprandial glucose levels at 60 min following a standard liquid meal test were reduced by 24-41 mg/dl vs. placebo. Saxagliptin was weight neutral. Adverse events were similar across treatment groups, including placebo, with a very low incidence of confirmed hypoglycaemia in saxagliptin treatment arms. CONCLUSIONS: Saxagliptin effectively improved glycaemic control in drug-naive patients with T2DM and was generally safe, with a tolerability profile similar to placebo. FAU - Rosenstock, J AU - Rosenstock J AD - Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX 75230, USA. juliorosenstock@dallasdiabetes.com FAU - Sankoh, S AU - Sankoh S FAU - List, J F AU - List JF LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20080318 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Dipeptides) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 9GB927LAJW (saxagliptin) RN - PJY633525U (Adamantane) SB - IM MH - Adamantane/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use MH - Adult MH - Aged MH - Blood Glucose/drug effects/metabolism MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dipeptides/administration & dosage/adverse effects/*therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/adverse effects/*therapeutic use MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Treatment Outcome EDAT- 2008/03/22 09:00 MHDA- 2008/08/05 09:00 CRDT- 2008/03/22 09:00 PHST- 2008/03/22 09:00 [pubmed] PHST- 2008/08/05 09:00 [medline] PHST- 2008/03/22 09:00 [entrez] AID - DOM876 [pii] AID - 10.1111/j.1463-1326.2008.00876.x [doi] PST - ppublish SO - Diabetes Obes Metab. 2008 May;10(5):376-86. doi: 10.1111/j.1463-1326.2008.00876.x. Epub 2008 Mar 18.