Table 2.

Subanalysis for the risk of diabetes mellitus with exposure to INSTIs in people living with HIV

Analysis	Arms	Studies (n)	References	INSTIs group (n)	Non-INSTIs group (n)	RR (95% CI)	Heterogeneity (I2), P value	Subgroup analysis: P value, heterogeneity (I2)	Interpretation of subgroup analysis
All studies	INSTIs versus PI and/or NNRTIs	13	27 30 38–41 43–49	27 610	44 794	0.80 (0.67 to 0.96)	29%	–	–
INSTI versus other drug classes	INSTI versus PI	6	27 30 39 41 43 47	24 771	21 049	0.78 (0.61 to 1.01)	27%	0.74, 0%	No subgroup effect, minimal heterogeneity
	INSTI versus NNRTI	7	27 30 38 40 45 46 48	10 350	17 842	0.75 (0.63 to 0.89)	0%
By ART status at baseline	ART-naïve	11	27 30 38–41 43–46 48	17 940	37 972	0.78 (0.65 to 0.94)	3%	0.29, 23%	No subgroup effect, minimal heterogeneity
	ART-experienced	2	47 49	8900	1389	0.85 (0.43 to 1.68)	0%
By presence of conflict of interest	Reported conflict of interest	9	30 38–40 43 45 47–49	22 522	21 801	0.85 (0.78 to 0.93)	0%	0.44, 23%	No subgroup effect, minimal heterogeneity
	No reported conflict of interest	4	27 41 44 46	5 088	22 993	0.65 (0.29 to 1.46)	59%
By age	Participants ≥18 years	11	27 30 38–41 43–46 49	11 798	42 371	0.77 (0.65 to 0.91)	26%	0.07, 29%	Statistically significant, qualitative subgroup effect
	Included participants below 18 years	2	47 48	15 812	2423	1.09 (0.13 to 9.29)	0%
By study setting	Multicenter	11	27 30 38–41 45–49	26 620	38 971	0.84 (0.77 to 0.93)	0%	<0.01, 23%	Statistically significant, quantitative subgroup effect
	Single center	2	43 44	990	5823	0.38 (0.13 to 1.11)	0%
By geographical origin of the study participants	Multinational	5	38–40 45 47	1309	1277	0.87 (0.81 to 0.94)	0%	<0.01, 13%	Statistically significant subgroup effect by region of origin, qualitative effect
	African	2	46 48	1000	650	2.99 (2.53 to 3.54)	0%
	North American	3	30 41 47	20 908	20 985	0.86 (0.53 to 1.42)	45%
	Europe	3	27 43 44	4393	21 882	0.54 (0.27 to 1.08)	3%
By study design	RCT	8	38–41 45 48 49	2912	3135	0.88 (0.81 to 0.96)	0%	0.27, 12%	No subgroup effect, minimal heterogeneity
	Cohort	5	27 30 43 44 47	24 698	41 659	0.69 (0.44 to 1.10)	60%
By primary outcome	Virological outcome	8	38–41 45 46 48 49	2912	3135	0.88 (0.81 to 0.96)	0%	0.16, 29%	No subgroup effect. Moderate heterogeneity.
	Metabolic outcome	5	27 30 43 44 47	24 698	41 659	0.69 (0.44 to 1.10)	60%
By follow-up duration	≥12 months	8	27 30 38 41 43–45 48	11 219	41 464	0.70 (0.53 to 0.94)	24%	0.07, 29%	No subgroup effect, minimal heterogeneity
	<12 months	6	39 40 45–47 49	16 460	3374	0.88 (0.79 to 0.99)	0%
By type of INSTI in ART-naïve patients	Dolutegravir	7	30 39 40 45–48	5751	17 679	0.94 (0.53 to 1.67)	43%	0.35, 61%	No subgroup effect, moderate heterogeneity
	Elvitegravir	2	30 47	5819	16 324	0.80 (0.01 to 123.82)	78%
	Raltegravir	4	30 38 41 47	2172	17 814	1.23 (0.91 to 1.66)	0%
By type of INSTI in ART-experienced patients	Dolutegravir	2	47 49	3889	1389	0.92 (0.21 to 3.99)	0%	0.57, 0%	No subgroup effect, minimal heterogeneity
	Elvitegravir	1	47	4281	1109	0.75 (0.48 to 1.17)	–
	Raltegravir	1	47	730	1109	1.09 (0.60 to 1.99)	–
By viral hepatitis comorbidities	Hepatitis B and C included	10	27 30 38–41 43–49	26 824	44 041	0.76 (0.58 to 1.00)	67.2%	0.88, 12%	No subgroup effect, minimal heterogeneity
	Only hepatitis C included	3	27 30 38–41 43–49	786	753	0.87 (0.78 to 0.98)	32.8%
By studies providing adjusted risk estimates		5				0.83 (0.58 to 1.18)	100%	–	–

the boldfaced values are Statistically significant.

.ART, antiretroviral therapy; INSTI, integrase strand transfer inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RCT, randomized controlled trial; RR, relative risk.