SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives

Figures & data

Figure1 Flow diagram of GLP-1 study selection.

Abbreviations: GLP-1RA, glucagon-like peptide-1 receptor agonists; RCT, randomized controlled trial; GLP-1, glucagon-like peptide-1.

Figure 2 Flow diagram of SGLT2-I study selection.

Abbreviations: SGLT2-I, sodium–glucose cotransporter 2 inhibitors; RCT, randomized controlled trial;

Table 1 Mean A1c reduction in clinical studies of GLP-1RA

Study	Duration (weeks)	Baseline A1c (%)	Treatment	Mean change in A1c (%)
Nauck et al^Citation21	26	8.4	LIRA 1.8 mg + MET	−1.0±0.1a
			LIRA 1.2 mg + MET	−1.0±0.1a
			LIRA 0.6 mg + MET	−0.7±0.1a
			Placebo + MET	+0.01±0.1
Vilsboll et al^Citation71	14	8.3	LIRA 1.9 mg	−1.45a
			LIRA 1.25 mg	−1.40a
			LIRA 0.65 mg	−0.98a
			Placebo	+0.29
Rosenstock et al^Citation23	16	8.0	ALBI 30 mg weekly	−0.87b
			ALBI 50 mg biweekly	−0.79b
			ALBI 100 mg monthly	−0.87b
			Placebo	−0.17
Grunberger et al^Citation20	12	7.7	DULA 1.5 mg weekly	−1.0±0.1a
			DULA 1.0 mg weekly	−1.0±0.1a
			DULA 0.5 mg weekly	−0.9±0.1a
			Placebo	0.0±0.1
Bolli et al^Citation25	24	8.0	LIXI one-step dose increase (10, 20 mg) + MET	−0.9±0.1c
			LIXI two-step dose increase (10, 15, 20 mg) + MET	−0.8±0.1c
			Placebo + MET	−0.4±0.1

Notes:

a P<0.001 vs placebo;

b P<0.003 vs placebo;

c P<0.0001 vs placebo.

Abbreviations: ALBI, albiglutide; DULA, dulaglutide; EXEN, exenatide; GLP-1RA, glucagon-like peptide-1 receptor agonists; LIRA, liraglutide; LIXI, lixisenatide; MET, metformin.

Table 2 Mean A1c reduction in clinical studies of SGLT2 inhibitors

Study	Duration (weeks)	Baseline A1c (%)	Treatment	Change in A1c (% +/− SD)
Bolinder et al^Citation55	102	7.2%	DAPA 10 mg + MET	−0.30
			Placebo + MET	+0.12 (95% CI −0.62 to −0.22)
Ferrannini et al^Citation51	12	7.9%	EMPA 25 mg + MET	−0.6a
			EMPA 10 mg + MET	−0.5a
			EMPA 5 mg + MET	−0.4a
			Placebo + MET	+0.1%
Haringet al^Citation53	24	7.9%	EMPA 25 mg + MET	−0.77±0.05a
			EMPA 10 mg + MET	−0.7±0.05a
			Placebo + MET	−0.13±0.05
Stenlofet al^Citation50	26	8%	CANA 300 mg	−1.03a
			CANA 100 mg	−0.77a
			Placebo	+0.14

Note:

a P<0.001 vs placebo.

Abbreviations: CANA, canagliflozin; CI, confidence interval; DAPA, dapagliflozin; EMPA, empagliflozin; MET, metformin; SGLT2, sodium–glucose cotransporter 2; SD, standard deviation.

Table 3 Special considerations: GLP-1 receptor antagonists and SGLT2 inhibitors

Outcome	GLP-1 receptor antagonists	SGLT2 inhibitors
A1c reduction (%)	0.7–1.7	0.32–1.17
Target of BG lowering	Shorter acting, mostly postprandial BG; longer acting, target fasting and postprandial BG	Fasting and postprandial BG
Hypoglycemia risk	Low	Low
Weight loss (kg)	2–5	1.5–3.0
Systolic blood pressure reduction (mmHg)	2–5	3–5
Cardiovascular outcomes	Unclear benefit in primary and secondary prevention	Reduction in CV death in patients with known ASCVD; unclear benefit in primary prevention
Potential adverse effects	Gastrointestinal upset, pancreatitis/pancreatic cancers, thyroid tumors/cancers, long-term safety not established	Genitourinary infections, diabetic ketoacidosis, bone fractures, long-term safety not established
Administration	Subcutaneous injections, twice daily to once weekly; may require reconstitution and use of prefilled pens	Oral, once daily
Cost/day (US $)^Citation72	13.56–21.37	12.10
Cost/QALYa^Citation64^–^Citation69	EXEN BID vs IG: dominate to £30,000	DAPA vs SITA: £6,800
	EXEN QW vs IG: £9,400–£13,000	DAPA vs MET: £2,700

Note:

a Range of findings.

Abbreviations: ASCVD, atherosclerotic cardiovascular disease; BG, blood glucose; BID, twice daily; CV, cardiovascular; DAPA, dapagliflozin; EXEN, exenatide; GLP-1, GLP-1, glucagon-like peptide-1; IG, insulin glargine; MET, metformin; QALY, quality-adjusted life year; QW; once weekly; SGLT2, sodium–glucose cotransporter 2; SITA, sitagliptin.

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