Relook at DPP-4 inhibitors in the era of SGLT-2 inhibitors

Table 1 HbA1c reduction with SGLT-2 inhibitors vs DPP-4 inhibitors

Ref.	Study duration (wk)	Background therapy	n (Active drug)	Baseline HbA1c	SGLT-2I (A) (% HbA1c reduction)	DPP-4I (B) (% HbA1c reduction)	∆ A minus B (95%CI)
HbA1c reduction with SGLT-2Is vs DPP-4Is in head-to-head randomized controlled trials
Rosenstock et al[2], 2012	12	Metformin	193	7.6%-7.8%	-0.76 (Cana 100 mg)	-0.74 (Sita 100 mg)	NC, (B) exploratory
					-0.92 (Cana 300 mg)
Roden et al[3], 2013	24	Drug naïve	671	7.9%	-0.66 (Empa 10 mg)	-0.66 (Sita 100 mg)	0.0 (-0.15, 0.14)
					-0.78 (Empa 25 mg)		-0.12 (-0.26, 0.03)
Rosenstock et al[4], 2013	12	Metformin	212	7.9%-8.1%	-0.56 (Empa 10 mg)	-0.45 (Sita 100 mg)	NC, (B) exploratory
					-0.55 (Empa 25 mg)
Ferrannini et al[5], 2013	90	Metformin	332	7.9%-8%	-0.34 (Empa 10 mg)	-0.40 (Sita 100 mg)	NC, (B) exploratory
					-0.63 (Empa 25 mg)
Lavalle-González et al[6], 2013	52	Metformin	1079	7.9%	-0.73 (Cana 100 mg)	-0.73 (Sita 100 mg)	-0.15a (-0.27, -0.03)
					-0.88 (Cana 300 mga)
Schernthaner et al[7], 2013	52	Metformin + SU	755	8.1%	-1.03 (Cana 300 mga)	-0.66 (Sita 100 mg)	-0.37a (-0.50, -0.25)
Amin et al[8], 2015	12	Metformin	328	8.1%	-0.80 (Ertu 5 mg)	-0.87 (Sita 100 mg)	NC, (B) exploratory
Difference in HbA1c reduction with SGLT-2Is vs DPP-4Is in meta-analyses
Pinto et al[9], 2015	≥ 12	LSM, Metformin, SU	NR (6 studies)	-	SGLT-2Is	DPP-4Is	-0.15a (-0.21, -0.08)
Maruthur et al[10], 2016	≤ 52	Metformin	1278 (4 studies)	-	SGLT-2Is	DPP-4Is	(B) minus (A) = +0.17a (0.08, 0.26)
Wang et al[11], 2018	12-78	Metformin	3454 (7 studies)	-	SGLT-2Is	DPP-4Is	(B) minus (A) = +0.11 (-0.03, 0.25)
Mishriky et al[12], 2018	≤ 26	Metformin	2462 (6 studies)	-	SGLT-2Is	DPP-4Is	(B) minus (A) = +0.05 (-0.05, 0.16)
	≥ 52	Metformin	1872 (3 studies)	-	SGLT-2Is	DPP-4Is	(B) minus (A) = +0.11a (0.03, 0.20)
HbA1c reduction with SGLT-2Is vs DPP-4Is in head-to-head randomized controlled trial stratified on baseline HbA1c
Rosenstock et al[13], 2015	24	Metformin	190	> 9%	-1.87 (Dapa 10 mg)	-1.32 (Saxa 5 mg)	NC
			103	< 8%	-0.45 (Dapa 10 mg)	-0.69 (Saxa 5 mg)
Lewin et al[14], 2015	24	LSM	116	≥ 8.5%	-1.66 (Empa 25 mg)	-1.07 (Lina 5 mg)	NC
					-1.54 (Empa 10 mg
			473	< 8.5%	-0.66 (Empa 25 mg)	-0.55 (Lina 5 mg)	NC
					-0.56 (Empa 10 mg)
DeFronzo et al[15], 2015	24	Metformin	101	≥ 8.5%	-1.22 (Empa 25 mg)	-0.99 (Lina 5 mg)	NC
					-1.29 (Empa 10 mg)
			508	< 8.5%	-0.43 (Empa 25 mg)	-0.62 (Lina 5 mg)	NC
					-0.46 (Empa 10 mg)

^a(A) superior over (B).

SGLT-2Is: SGLT-2 inhibitors; DPP-4Is: DPP4 inhibitors; Cana: Canagliflozin; Empa: Empagliflozin; Dapa: Dapagliflozin; Ertu: Ertugliflozin; Sita: Sitagliptin; Saxa: Saxagliptin; Lina: Linagliptin; SU: Sulfonylureas; LSM: Life style modification; NC: Not compared.