J Hans DeVries1, Luigi Meneghini2, Anthony H Barnett3, Timothy Reid4, Marie-Paule Dain5, Wolfgang Landgraf6, Aleksandra Vlajnic7, Louise Traylor7, Richard M Bergenstal8. 1. Consultant Endocrinologist, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 2. Professor, University of Texas Southwestern Medical Center, Dallas, Texas, US. 3. Honorary Consultant and Professor of Medicine, Heart of England NHS Foundation Trust and University of Birmingham, Birmingham, UK. 4. Medical Director, Mercy Diabetes Center, Janesville, Wisconsin, US. 5. Sanofi, Paris, France. 6. Sanofi, Frankfurt, Germany and Third Medical Clinic, University of Dresden, Dresden, Germany. 7. Sanofi US Inc., Bridgewater, New Jersey, US. 8. Executive Director and Research Clinician, International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, US.
Abstract
Background: A better understanding of hypoglycaemia risk when insulin is used in combination with one or more oral antidiabetes agents may assist in the treatment decision-making process for the clinician and address concerns regarding hypoglycaemia when initiating or intensifying insulin therapy. The objective of this study was to analyse efficacy and hypoglycaemia outcomes in people with type 2 diabetes receivinginsulin glargine (IG) with metformin (MET), sulphonylurea (SU) or MET+SU. Methods: Patient-level data were pooled from 15 randomised, treat-to-target trials (fasting plasma glucose [FPG] targets <5.6 mmol/l) with a duration >24 weeks. Efficacy outcomes included glycated haemoglobin (HbA1c), FPG and HbA1c target achievement. Overall hypoglycaemia events were assessed by a confirmed PG value of <3.9, <3.1 and <2.8 mmol/l or assistance required; daytime, nocturnal (00:01-05:59 AM); and severe (assistance required or with confirmed PG <2.0 mmol/l). Results: Overall, 2,837 IG patients were analysed, with either MET (634), SU (906) or MET+SU (1,297) as background oral antidiabetes agents. Endpoint HbA1c in IG+MET and IG+MET+SU-treated patients was significantly lower than in IG+SU-treated patients (adjusted difference -0.32 %; p=0.0001 and -0.33 %; p=0.0002, respectively). Fewer patients achieved endpoint HbA1c <7.0 % with IG+SU (32 %) versus IG+MET (57 %) or IG+MET+SU (49 %). IG+SU and IG+MET+SU led to significant increases in overall, daytime and nocturnal hypoglycaemia versus IG+MET; severe hypoglycaemia was rare. Weight gain was lowest in IG+MET patients (adjusted difference -1.51 kg versus IG+SU; p<0.0001; -0.78 kg versus IG+MET+SU; p=0.0037) despite higher insulin doses (0.51 U/kg versus 0.43 and 0.42 U/kg, respectively). Conclusions: Better glycaemic goal achievement and reduced risk of hypoglycaemia and weight gain were observed with IG+MET versus IG+SU and IG+MET+SU, albeit with an increased insulin dose requirement.
RCT Entities:
Background: A better understanding of hypoglycaemia risk when insulin is used in combination with one or more oral antidiabetes agents may assist in the treatment decision-making process for the clinician and address concerns regarding hypoglycaemia when initiating or intensifying insulin therapy. The objective of this study was to analyse efficacy and hypoglycaemia outcomes in people with type 2 diabetes receiving insulinglargine (IG) with metformin (MET), sulphonylurea (SU) or MET+SU. Methods:Patient-level data were pooled from 15 randomised, treat-to-target trials (fasting plasma glucose [FPG] targets <5.6 mmol/l) with a duration >24 weeks. Efficacy outcomes included glycated haemoglobin (HbA1c), FPG and HbA1c target achievement. Overall hypoglycaemia events were assessed by a confirmed PG value of <3.9, <3.1 and <2.8 mmol/l or assistance required; daytime, nocturnal (00:01-05:59 AM); and severe (assistance required or with confirmed PG <2.0 mmol/l). Results: Overall, 2,837 IG patients were analysed, with either MET (634), SU (906) or MET+SU (1,297) as background oral antidiabetes agents. Endpoint HbA1c in IG+MET and IG+MET+SU-treated patients was significantly lower than in IG+SU-treated patients (adjusted difference -0.32 %; p=0.0001 and -0.33 %; p=0.0002, respectively). Fewer patients achieved endpoint HbA1c <7.0 % with IG+SU (32 %) versus IG+MET (57 %) or IG+MET+SU (49 %). IG+SU and IG+MET+SU led to significant increases in overall, daytime and nocturnal hypoglycaemia versus IG+MET; severe hypoglycaemia was rare. Weight gain was lowest in IG+MET patients (adjusted difference -1.51 kg versus IG+SU; p<0.0001; -0.78 kg versus IG+MET+SU; p=0.0037) despite higher insulin doses (0.51 U/kg versus 0.43 and 0.42 U/kg, respectively). Conclusions: Better glycaemic goal achievement and reduced risk of hypoglycaemia and weight gain were observed with IG+MET versus IG+SU and IG+MET+SU, albeit with an increased insulin dose requirement.
Entities:
Keywords:
Insulin therapy; metformin; sulphonylurea; type 2 diabetes
Authors: L A Donnelly; A D Morris; B M Frier; J D Ellis; P T Donnan; R Durrant; M M Band; G Reekie; G P Leese Journal: Diabet Med Date: 2005-06 Impact factor: 4.359
Authors: Peter Mullins; Peter Sharplin; Hannele Yki-Jarvinen; Matthew C Riddle; Hans-Ulrich Haring Journal: Clin Ther Date: 2007-08 Impact factor: 3.393
Authors: Silvio E Inzucchi; Richard M Bergenstal; John B Buse; Michaela Diamant; Ele Ferrannini; Michael Nauck; Anne L Peters; Apostolos Tsapas; Richard Wender; David R Matthews Journal: Diabetes Care Date: 2012-04-19 Impact factor: 19.112