PMID- 33313996
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230919
IS  - 1869-6953 (Print)
IS  - 1869-6961 (Electronic)
IS  - 1869-6961 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Jan
TI  - Comparative Efficacy of Dual and Single Initiation of Add-On Oral 
      Antihyperglycemic Agents in Type 2 Diabetes Uncontrolled on Metformin Alone: A 
      Systematic Literature Review and Network Meta-Analysis.
PG  - 389-418
LID - 10.1007/s13300-020-00975-y [doi]
AB  - INTRODUCTION: Current guidelines recommend adding an oral antihyperglycemic agent 
      (AHA) to metformin in patients with type 2 diabetes mellitus (T2DM) uncontrolled 
      on metformin. Recent randomized clinical trials (RCTs) have demonstrated that 
      adding dual AHAs instead of a single AHA provided more effective glycemic 
      control. However, the comparative efficacy of approved single and dual initiation 
      strategies is unknown. Therefore, we conducted a Bayesian network meta-analysis 
      to compare the efficacy of dual and single add-on oral AHAs in patients 
      uncontrolled on metformin. METHODS: A systematic literature review of RCTs was 
      conducted following Cochrane and ISPOR guidelines. MEDLINE, Embase, and CENTRAL 
      were searched from inception to November 19, 2019. Approved oral doses of 
      sodium-glucose co-transporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 
      (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in 
      single or dual initiation therapies were indirectly compared. Outcomes focused on 
      efficacy and included mean change from baseline in hemoglobin A1c (HbA1c), 
      weight, systolic blood pressure (SBP), diastolic blood pressure, and achieving 
      HbA1c target < 7% at 24-26 weeks. Fixed and random effects models with Markov 
      chain Monte Carlo simulations were used. RESULTS: Of 1955 unique records 
      screened, 25 RCTs (14,264 participants) were included. In patients uncontrolled 
      on metformin, dual AHA added to metformin had statistically significant or a 
      trend of greater reduction in HbA1c compared to single AHAs, with 
      ertugliflozin + sitagliptin showing the greatest improvement. Statistically 
      significant reductions in weight and SBP were observed with 
      ertugliflozin + sitagliptin, ertugliflozin, or canagliflozin compared to single 
      initiation DPP-4 inhibitors. CONCLUSION: For reduction of HbA1c, weight, and SBP 
      in patients uncontrolled on metformin, add-on dual AHAs showed greater 
      improvement compared to single AHAs. These findings can further inform the 
      treatment of T2DM patients uncontrolled on metformin.
FAU - Lautsch, Dominik
AU  - Lautsch D
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, 
      USA. dominik.lautsch@merck.com.
FAU - Alsumali, Adnan
AU  - Alsumali A
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, 
      USA.
FAU - McLeod, Euan
AU  - McLeod E
AD  - Pfizer, Inc., Tadworth, UK.
FAU - Kuang, Yuting
AU  - Kuang Y
AD  - IQVIA, Inc., San Francisco, CA, USA.
FAU - He, Jing
AU  - He J
AD  - IQVIA, Inc., San Francisco, CA, USA.
FAU - Singh, Rajpal
AU  - Singh R
AD  - IQVIA, Inc., Mumbai, India.
FAU - Nevo, Arianna
AU  - Nevo A
AD  - IQVIA, Inc., San Francisco, CA, USA.
FAU - Arnet, Urs
AU  - Arnet U
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, 
      USA.
FAU - Uyei, Jennifer
AU  - Uyei J
AD  - IQVIA, Inc., San Francisco, CA, USA.
FAU - Rajpathak, Swapnil
AU  - Rajpathak S
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20201212
PL  - United States
TA  - Diabetes Ther
JT  - Diabetes therapy : research, treatment and education of diabetes and related 
      disorders
JID - 101539025
PMC - PMC7843850
OTO - NOTNLM
OT  - Dual initiation
OT  - Network meta-analysis
OT  - Oral antihyperglycemic agent
OT  - Type 2 diabetes
EDAT- 2020/12/15 06:00
MHDA- 2020/12/15 06:01
PMCR- 2020/12/12
CRDT- 2020/12/14 11:04
PHST- 2020/10/20 00:00 [received]
PHST- 2020/11/19 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2020/12/15 06:01 [medline]
PHST- 2020/12/14 11:04 [entrez]
PHST- 2020/12/12 00:00 [pmc-release]
AID - 10.1007/s13300-020-00975-y [pii]
AID - 975 [pii]
AID - 10.1007/s13300-020-00975-y [doi]
PST - ppublish
SO  - Diabetes Ther. 2021 Jan;12(1):389-418. doi: 10.1007/s13300-020-00975-y. Epub 2020 
      Dec 12.