PMID- 32745202
OWN - NLM
STAT- MEDLINE
DCOM- 20210219
LR  - 20221207
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 105
IP  - 10
DP  - 2020 Oct 1
TI  - Improved Beta Cell Glucose Sensitivity Plays Predominant Role in the Decrease in 
      HbA1c with Cana and Lira in T2DM.
LID - dgaa494 [pii]
LID - 10.1210/clinem/dgaa494 [doi]
AB  - AIM: To examine the effect of combination therapy with canagliflozin plus 
      liraglutide versus each agent alone on beta cell function in type 2 diabetes 
      mellitus (T2DM) patients. RESEARCH DESIGN AND METHODS: A total of 45 poorly 
      controlled (HbA1c = 7%-11%) T2DM patients received an oral glucose tolerance test 
      (OGTT) before and after 16 weeks of treatment with: (i) liraglutide (LIRA); (ii) 
      canagliflozin (CANA); (iii) liraglutide plus canagliflozin (CANA/LIRA). RESULTS: 
      Both liraglutide and canagliflozin significantly lowered HbA1c with no 
      significant additive effect of the combination on HbA1c (0.89%, 1.43%, and 1.67% 
      respectively). Insulin secretion during the OGTT, measured with (∆C-Pep/∆G)0-120, 
      increased in the 3 groups (from 0.30 +/- 0.06 to 0.48 +/- 0.10; 0.29 +/- 0.05 to 0.98 +/- 
      0.23; and 0.24 +/- 0.06 to 1.09 +/- 0.12 in subjects receiving CANA, LIRA and 
      CANA/LIRA respectively; P = 0.02 for CANA vs LIRA, P < 0.0001, CANA/LIRA vs 
      CANA), and the increase in insulin secretion was associated with an increase in 
      beta cell glucose sensitivity (29 +/- 5 to 55 +/- 11; 33 +/- 6 to 101 +/- 16; and 28 +/- 6 
      to 112 +/- 12, respectively; P = 0.01 for CANA vs LIRA, P < 0.0001, CANA/LIRA vs 
      CANA). No significant difference in the increase in insulin secretion or beta 
      cell glucose sensitivity was observed between subjects in LIRA or CANA/LIRA 
      groups. The decrease in HbA1c strongly and inversely correlated with the increase 
      in beta cell glucose sensitivity (r = 0.71, P < 0.001). In multivariate 
      regression model, improved beta cell glucose sensitivity was the strongest 
      predictor of HbA1c decrease with each therapy. CONCLUSION: Improved beta cell 
      glucose sensitivity with canagliflozin monotherapy and liraglutide monotherapy or 
      in combination is major factor responsible for the HbA1c decrease. Canagliflozin 
      failed to produce an additive effect to improve beta cell glucose sensitivity 
      above that observed with liraglutide.
CI  - Published by Oxford University Press on behalf of the Endocrine Society 2020.
FAU - Ali, Ali Muhammed
AU  - Ali AM
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Mari, Andrea
AU  - Mari A
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Martinez, Robert
AU  - Martinez R
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Al-Jobori, Hussein
AU  - Al-Jobori H
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Adams, John
AU  - Adams J
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Triplitt, Curtis
AU  - Triplitt C
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - DeFronzo, Ralph
AU  - DeFronzo R
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Cersosimo, Eugenio
AU  - Cersosimo E
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
FAU - Abdul-Ghani, Muhammad
AU  - Abdul-Ghani M
AD  - Division of Diabetes, University of Texas Health Science Center, San Antonio, 
      Texas.
LA  - eng
SI  - ClinicalTrials.gov/NCT02324842
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 839I73S42A (Liraglutide)
SB  - IM
CIN - J Clin Endocrinol Metab. 2020 Dec 1;105(12):. PMID: 33074334
MH  - Blood Glucose/analysis/drug effects/metabolism
MH  - Canagliflozin/*administration & dosage
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy
MH  - Drug Therapy, Combination/methods
MH  - Female
MH  - Glucose Tolerance Test
MH  - Glycated Hemoglobin/*analysis
MH  - Humans
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Liraglutide/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
OTO - NOTNLM
OT  - beta cell function
OT  - canagliflozin
OT  - insulin secretion
OT  - liraglutide
EDAT- 2020/08/04 06:00
MHDA- 2021/02/20 06:00
CRDT- 2020/08/04 06:00
PHST- 2020/01/08 00:00 [received]
PHST- 2020/07/31 00:00 [accepted]
PHST- 2020/08/04 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
PHST- 2020/08/04 06:00 [entrez]
AID - 5880025 [pii]
AID - 10.1210/clinem/dgaa494 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa494. doi: 10.1210/clinem/dgaa494.