Opinion Review
Copyright ©The Author(s) 2022.
World J Cardiol. Jun 26, 2022; 14(6): 329-342
Published online Jun 26, 2022. doi: 10.4330/wjc.v14.i6.329
Table 1 Studies with GLP-1 receptor agonists plus SGLT-2 inhibitors vs SGLT-2 inhibitors or GLP-1 receptor agonists
Type of study
Ref.
Comparator agent
n
Duration
∆HbA1c (%), (95%CI or mean ± SD)
∆Weight (kg), (95%CI)
∆SBP (mmHg), (95%CI)
OR for severe Hypo’s (95%CI)
GI S/E
GTI
Simultaneous initiation of GLP-1RA plus SGLT-2I vs SGLT-2I
RCT, DB/ DURATION-8Frías et al[16], 2016EXE QW + DAPA vs DAPA69528 wk-0.6 (-0.8; -0.3)-1.22 (-2.00; -0.44)-2.4 (-4.5; -0.3)1.00 (0.02; 50.61)EXENA + DAPA-16%; DAPA-12%EXENA + DAPA- 4%; DAPA- 6%
RCTIkonomodis et al[19], 2018LIRA + EMPA vs EMPA4012 wk-0.70 (-2.55; 1.15)NR0.00 (-5.70; 5.70)NRNRNR
RCT, OLAli et al[12], 2020LIRA + CANA vs CANA4516 wk-0.78 (-1.52; -0.04)-2.50 (-4.35; -0.65)-8.90 (-16.19; -1.61)1.00 (0.02; 53.66)NRNR
Sequential addition of GLP-1RA to SGLT-2I vs SGLT-2I
RCT, DB/AWARD-10Ludvik et al[20], 2018DULA + SGLT-2I vs PBO + SGLT-2I42424 wk-0.73 (-0.88; -0.58)-0.75 (-1.47; -0.03)-2.45 (-4.78; -0.12)2.50 (0.06; 104.85)DULA + SGLT-2I- 26.5%; PBO-17%DULA + SGLT-2I- 0%; PBO-1%
RCT, DB/SUSTAIN-9Zinman et al[21], 2019SEMA + SGLT-2I vs PBO + SGLT-2I30230 wk-1.40 (-1.58; -1.22)-3.80 (-4.67; -2.93)-6.30 (-9.07; -3.53)9.27 (0.50; 173.02)SEMA + SGLT-2I- 37.3%; PBO-13.2%NR
RCT, DB/LIRA-ADD2SGLT2iBlonde et al[22], 2020LIRA + SGLT-2I vs PBO + SGLT-2I30326 wk-0.68 (-0.89; -0.47)-0.82 (-1.67; 0.03)1.40 (-1.65; 4.45)1.00 (0.02; 64.81)LIRA + SGLT-2I- 26%1; PBO-6.0%1NR
Simultaneous initiation of SGLT-2I plus GLP-1RA vs GLP-1RA
RCT/DURATION-8Frías et al[16], 2016DAPA + EXE QW vs EXE QW69528 wk-0.4 (-0.6; -0.1)-1.87 (-2.66; -1.08)-2.9 (-5.0; -0.8)1.00 (0.02; 50.61)EXENA + DAPA-16%; DAPA-15%EXENA + DAPA-4%; EXENA-2%
RCTIkonomodis et al[19], 2018EMPA + LIRA vs LIRA4012 wk-0.20 (-2.16; 1.76)NR-1.00 (-6.57; 4.57)NRNRNR
RCTAli et al[12], 2020CANA + LIRA vs LIRA4516 wk-0.23 (-1.18; 0.72)-4.10 (-6.32; -1.88)-9.00 (-18.49; 0.49)1.00 (0.02; 53.66)NRNR
Sequential addition of SGLT-2I to GLP-1RA vs GLP-1RA
RCT, DB/CANVASFulcher et al[23], 2016CANA + GLP-1RA vs PBO + GLP-1RA9518 wk-1.03 (-1.34; -0.72)-2.72 (-3.70; -1.74)-8.05 (-14.13; -1.97)2.5 (0.05; 114.6)NRCANA + GLP-1RA-12.3%; PBO-5.3%
Non-randomized studies (all ∆ from baseline)
Simultaneous initiation of SGLT-2I plus GLP-1RA
ObsGoncalves et al[28,29], 2017SGLT-2I with LIRA3362-2.0-10.0-13.0NRNRNR
Sequential addition of SGLT-2I to GLP-1RA
ObsSaroka et al[24], 2015CANA added to GLP-1RA75 (60 on insulin)10.7 mo (mean)-0.39 ± 0.88-4.6 ± 4.3-4.0 ± 12NR1.3%GTI: 8%
Retro, ObsCurtis et al[25], 2016DAPA added to GLP-1RA14 (10 on insulin)48 wk-4.4 (-5.7; -2.7)-5.47 (-22.9; -5)NRNRNRNR
Retro, ObsDeol et al[26], 2016SGLT-2I added to GLP-1RA37 (DAPA = 36, CANA = 1)3-6 mo 139 d (mean)-1.05 (-1.41; -0.69)-3.07 (-4.36; -1.78)-1.16 (-6.01; 8.42)NRNRNR
Non-R, OL, PMSHarashima et al[27], 2017CANA added to LIRA7152 wk-0.7 (-0.89; -0.51)-3.29 (-3.86; -2.72)-7.9 (-10.7; -5.1)9.9% (mild)NR7.1%
ObsGoncalves et al[28,29], 2017SGLT-2I added to LIRA4676 wk-0.9-4.0-7.0NRNRNR
Non-RSeino et al[30], 2018LUSEO added to LIRA7652 wk-0.68 (-0.87; -0.49)-2.71 (-3.18; -2.23)-7.1 (-10.4; -3.9)6.6% (mild)13.2%3.9%
1Nausea. CANA: Canagliflozin; DAPA: Dapagliflozin; DB: Double blind; EMPA: Empagliflozin; EX QW: Exenatide once weekly; GI: Gastrointestinal; GLP-1RA: GLP-1 receptor agonists; GTI: Genital tract infections; Hypo’s: Hypoglycemia; LIRA: Liraglutide; LUSEO: Luseogliflozin; Non-R: Non-randomized; NR: Not reported/retrievable; Obs: Observational; OL: Open label; OR: Odds ratio; PBO: Placebo; PMS: Post marketing study; RCT: Randomized controlled trial; Retro: Retrospective; SBP: Systolic blood pressure; SGLT-2I: SGLT-2 inhibitors; S/E: Side effect; SEMA: Semaglutide.