PMID- 33594488
OWN - NLM
STAT- MEDLINE
DCOM- 20210827
LR  - 20210827
IS  - 1433-2965 (Electronic)
IS  - 0937-941X (Linking)
VI  - 32
IP  - 9
DP  - 2021 Sep
TI  - Effect of metformin and insulin vs. placebo and insulin on whole body composition 
      in overweight patients with type 2 diabetes: a randomized placebo-controlled 
      trial.
PG  - 1837-1848
LID - 10.1007/s00198-021-05870-1 [doi]
AB  - Some studies indicate potential beneficial effects of metformin on body 
      composition and bone. This trial compared metformin + insulin vs placebo + 
      insulin. Metformin treatment had a small but positive effect on bone quality in 
      the peripheral skeleton, reduced weight gain, and resulted in a more beneficial 
      body composition compared with placebo in insulin-treated patients with type 2 
      diabetes. INTRODUCTION: Glucose-lowering medications affect body composition. We 
      assessed the long-term effects of metformin compared with placebo on whole body 
      bone and body composition measures in patients with type 2 diabetes mellitus. 
      METHODS: This was a sub-study of the Copenhagen Insulin and Metformin Therapy 
      trial, which was a double-blinded randomized placebo-controlled trial assessing 
      18-month treatment with metformin compared with placebo, in combination with 
      different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The 
      sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and 
      body composition from whole body dual-energy X-ray absorptiometry (DXA) scans 
      which were assessed at baseline and after 18 months. RESULTS: Metformin had a 
      small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC 
      and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, 
      BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and 
      BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD 
      corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 
      0.4% and 0.4% decrease in the placebo group, respectively. These effects were 
      mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD 
      in the arms. During 18 months, all participants increased in weight, fat mass 
      (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group 
      increased less in weight (subtotal weight (weight-head) - 2.4 [- 3.5, - 1.4] kg, 
      p value < 0.001) and FM (- 1.5 [- 2.3, - 0.8] kg, p value < 0.001) and decreased 
      less in LM% (0.6 [0.2, 1.1] %, p value < 0.001) compared with the placebo group. 
      CONCLUSION: Metformin treatment had a small positive effect on BMC and BMD in the 
      peripheral skeleton and reduced weight gain compared with placebo in 
      insulin-treated patients with T2DM.
CI  - (c) 2021. International Osteoporosis Foundation and National Osteoporosis 
      Foundation.
FAU - Nordklint, A K
AU  - Nordklint AK
AUID- ORCID: 0000-0003-1448-618X
AD  - Department of Nephrology and Endocrinology, Nordsjaellands University Hospital, 
      Hillerod, Denmark. azrica87@gmail.com.
AD  - Department of Ophthalmology, Rigshopitalet - Glostrup, Copenhagen, Denmark. 
      azrica87@gmail.com.
FAU - Almdal, T P
AU  - Almdal TP
AD  - Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
AD  - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 
      Denmark.
FAU - Vestergaard, P
AU  - Vestergaard P
AD  - Departments of Clinical Medicine and Endocrinology, Aalborg University Hospital, 
      Aalborg, Denmark.
AD  - Steno Diabetes Center North Jutland, Aalborg, Denmark.
FAU - Lundby-Christensen, L
AU  - Lundby-Christensen L
AD  - Steno Diabetes Center Zealand, Holbak, Denmark.
FAU - Boesgaard, T W
AU  - Boesgaard TW
AD  - Steno Diabetes Center Copenhagen, Gentofte, Denmark.
FAU - Breum, L
AU  - Breum L
AD  - Department of Medicine, Zealand University Hospital, Koge, Denmark.
FAU - Gade-Rasmussen, B
AU  - Gade-Rasmussen B
AD  - Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark.
FAU - Sneppen, S B
AU  - Sneppen SB
AD  - Department of Medicine, Gentofte, Copenhagen University Hospital, Hellerup, 
      Denmark.
FAU - Gluud, C
AU  - Gluud C
AD  - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, 
      Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Hemmingsen, B
AU  - Hemmingsen B
AD  - Department of Nephrology and Endocrinology, Nordsjaellands University Hospital, 
      Hillerod, Denmark.
AD  - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, 
      Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Perrild, H
AU  - Perrild H
AD  - Department of Endocrinology, Bispebjerg, Copenhagen University Hospital, 
      Copenhagen, Denmark.
FAU - Madsbad, S
AU  - Madsbad S
AD  - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 
      Denmark.
AD  - Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark.
FAU - Mathiesen, E R
AU  - Mathiesen ER
AD  - Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
AD  - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 
      Denmark.
FAU - Tarnow, L
AU  - Tarnow L
AD  - Steno Diabetes Center Zealand, Holbak, Denmark.
FAU - Thorsteinsson, B
AU  - Thorsteinsson B
AD  - Department of Nephrology and Endocrinology, Nordsjaellands University Hospital, 
      Hillerod, Denmark.
AD  - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 
      Denmark.
FAU - Vestergaard, H
AU  - Vestergaard H
AD  - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 
      Denmark.
AD  - Department of Medicine, Bornholms Hospital, Ronne, Denmark.
AD  - The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of 
      Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark.
FAU - Lund, S S
AU  - Lund SS
AD  - Steno Diabetes Center Copenhagen, Gentofte, Denmark.
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Eiken, P
AU  - Eiken P
AD  - Department of Nephrology and Endocrinology, Nordsjaellands University Hospital, 
      Hillerod, Denmark.
AD  - Department of Endocrinology, Bispebjerg, Copenhagen University Hospital, 
      Copenhagen, Denmark.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20210216
PL  - England
TA  - Osteoporos Int
JT  - Osteoporosis international : a journal established as result of cooperation 
      between the European Foundation for Osteoporosis and the National Osteoporosis 
      Foundation of the USA
JID - 9100105
RN  - 0 (Insulin)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Body Composition
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Humans
MH  - Insulin
MH  - *Metformin/therapeutic use
MH  - Overweight
OTO - NOTNLM
OT  - Body composition
OT  - Bone mineral content
OT  - Bone mineral density
OT  - Fat mass
OT  - Insulin
OT  - Lean mass
OT  - Metformin
OT  - Osteoporosis
OT  - Type 2 diabetes mellitus
EDAT- 2021/02/18 06:00
MHDA- 2021/08/28 06:00
CRDT- 2021/02/17 05:58
PHST- 2020/04/20 00:00 [received]
PHST- 2021/02/01 00:00 [accepted]
PHST- 2021/02/18 06:00 [pubmed]
PHST- 2021/08/28 06:00 [medline]
PHST- 2021/02/17 05:58 [entrez]
AID - 10.1007/s00198-021-05870-1 [pii]
AID - 10.1007/s00198-021-05870-1 [doi]
PST - ppublish
SO  - Osteoporos Int. 2021 Sep;32(9):1837-1848. doi: 10.1007/s00198-021-05870-1. Epub 
      2021 Feb 16.