Table 1

Randomised comparative studies included in NMA of patients with T2DM on basal insulin treatment

	First author, year published (Regimen type)	Countries/Continents	Key inclusion criteria	N*	Randomised comparator arms	Allocation method	Study duration	Discontinuation rate†	Outcomes in current NMA‡
	First author, year published (Regimen type)	Countries/Continents	Key inclusion criteria	N*	Randomised comparator arms	Allocation method	Study duration	Discontinuation rate†	A	B	C	D
Gla-300 vs Gla-100	Bolli, 20158	North America, Europe, Japan	Insulin naïve OAD HbA1c 7–11%	873	Gla-300 Gla-100	IVRS	6 months	Gla-300: 62/439 (14%) Gla-100: 75/439 (17%)	✓	✓	✓	✓
	Riddle, 20146	North America, Europe, South Africa	On basal bolus insulin regimen HbA1c 7–10%	806	Gla-300 + bolus Gla-100 + bolus	IVRS	6 months	Gla-300: 30/404 (7.4%) Gla-100: 31/402 (7.7%)	✓	✓	✓	✓
	Yki-Järvinen, 20147	North America, Europe, Russia, South America, South Africa	On basal insulin OAD HbA1c 7–10%	809	Gla-300 Gla-100	IVRS	6 months	Gla-300: 36/404 (8.9%) Gla-100: 38/407 (9.3%)	✓	✓	✓	✓
Gla-100 vs premixed insulin	Aschner, 201310	NR	Insulin naïve OAD	923	Premixed Gla-100±glulisine	NR	24 weeks	NR (meeting abstract)	✓	✓		✓
	Buse, 200911	Australia, Europe, India, North America, South America	Insulin naïve OAD HbA1c >7%	2091	Lispro protamine/lispro 75/25 Gla-100	IVRS	24 weeks	Premixed insulin:145/1045 (13.9%) Gla-100: 128/1046 (12.2%)	✓	✓
	Fritsche, 201012	Europe and Australia	Premixed insulin +/- Metformin HbA1c 7.5–11.0%	310	70/30 NPH + bolus (regular or aspart) Gla-100 + glulisine	Electronic case record system	52 weeks	Premixed insulin: 28/157 (17.8%) Gla-100:25/153 (16.3%)	✓	✓	✓
	Jain, 201013	Asia, Australia, Europe, North America, Russian Federation	Insulin naïve OAD HbA1c ≥7.5–12%	484	Insulin lispro 50/50 Gla-100 + lispro	TS	36 weeks	Premixed insulin: 31/242 (12.8%) Gla-100: 27/242 (11.2%)	✓	✓
	Kann, 200614	Europe	Insulin naïve OAD HbA1c >7–12%	255	Insulin aspart 70/30+ metformin Gla-100 + glimepiride	Sealed codes	28 weeks	Premixed insulin: 13/130 (10.0%) Gla-100: 12/128 (9.4%)	✓	✓
	Kazda, 200615	Germany	Insulin naïve HbA1c 6–10.5%	159	Protaminatedlispro/lispro 50/50 Lispro Gla-100	NR	24 weeks	Premixed insulin: 14.8%§ Bolus insulin: 7.7%§ Gla-100: 15.1%§	✓	✓
	Ligthelm, 201116	USA and Puerto Rico	On basal insulin OAD HbA1c ≥8%	279	Biphasic aspart 70/30 Gla-100	IVRS	24 weeks	Premixed insulin: 19/137 (13.9%) Gla-100: 32/143 (22.4%)	✓	✓	✓
	Raskin, 200517	USA	Insulin naïve OAD HbA1c ≥8%	222	Biphasic aspart 70/30 Gla-100	Sequential numbers/codes	28 weeks	Premixed insulin:17/117 (14.5%) Gla-100: 7/116 (6.0%)	✓
	Riddle, 201118	NR	OAD	572	Protamine-aspart/aspart 70/30 Glargine + 1 prandial Glulisine Gla-100 + glulisine (stepwise addition)	NR	60 weeks	NR (meeting abstract)	✓			✓
	Robbins, 200719	Australia, Europe, India, North America (USA and Puerto Rico)	OAD HbA1c 6.5–11%	315	Lispro 50/50 + metformin Gla-100+metformin	TS	24 weeks	Premixed insulin: 15/158 (9.5%) Gla-100: 22/159 (13.8%)	✓	✓
	Rosenstock, 200820	USA and Puerto Rico	On basal insulin OAD HbA1c 7.5–12%	374	Insulin lispro protamine/lispro Gla-100 + lispro	TS	24 weeks	Premixed insulin: 29/187 (15.5%) Gla-100: 29/187 (15.5%)	✓	✓		✓
	Strojek, 200921	Asia, Europe, North America, South America, South Africa	Insulin naïve OAD HbA1c >7–11%	469	Biphasic aspart 70/30 + metformin/glimepiride Gla-100 +metformin/glimepiride	IVRS	26 weeks	Premixed insulin: 26/239 (10.9%) Gla-100: 21/241 (8.7%)	✓		✓
	Tinahones, 201322	11 countries (not specified)	On basal insulin OAD HbA1c 7.5–10.5%	478	Lispro mix 25/75 Gla-100 + lispro	NR	24 weeks	NR (meeting abstract)	✓	✓		✓
	Vora, 201323	NR	On basal insulin	335	Biphasic insulin aspart/aspart protamine 30/70 Gla-100 + glulisine	NR	24 weeks	Premixed insulin: 23/165 (13.9%) Gla-100: 14/170 (8.2%)	✓			✓
Gla-100 vs NPH	Fritsche, 200324	Europe	Insulin naïve OAD HbA1c 7.5–10.5%	695	NPH Gla-100 (morning) Gla-100 (bedtime)	Sequential numbers/codes	28 weeks	NPH: 27/234 (11.5%) Gla-100 (morning): 12/237 (5.1%) Gla-100 (bedtime):18/229 (7.9%)	✓	✓		✓
	Massi Benedetti, 200325	Europe, South Africa	OAD	570	NPH Gla-100	Sequential numbers/codes	52 weeks	NPH: 33/285(11.6%) Gla-100: 16/293 (5.5%)	✓			✓
	Riddle, 200326	North America	Insulin naïve OAD HbA1c 7.5–10%	756	NPH Gla-100	IVRS	24 weeks	NPH: 32/392 (8.2%) Gla-100: 33/372 (8.9%)	✓	✓		✓
	Rosenstock, 200127	NR	On insulin HbA1c 7–12%	518	NPH Gla-100	NR	28 weeks	NPH: 21/259 (8.1%) Gla-100: 28/259 (10.8%)	✓	✓		✓
	Rosenstock 200928	North America	OAD HbA1c 6–12%	1017	NPH Gla-100	IVRS	5 years	NPH: 145/509 (28.5%)§ Gla-100: 141/515 (27.4%)§	✓	✓
	Yki-Järvinen, 200629	Europe	Insulin naïve OAD HbA1c ≥8%	110	NPH Gla-100	NR	36 weeks	NPH: 1/49 (2.0%) Gla-100: 1/61 (1.6%)	✓	✓		✓
Degludec vs Gla-100	Garber, 201230	Asia (Hong Kong), Europe, Middle East (Turkey), North America, Russia, South Africa	On insulin ±OAD HbA1c 7–10%	1004	Degludec + aspart Gla-100 + aspart	IVRS	52 weeks	Degludec: 137/755 (18.1%) Glargine:40/251 (15.9%)	✓	✓	✓	✓
	Gough, 201331	Europe, North America, Russia, South Africa	Insulin naïve OAD HbA1c 7–10%	456	Degludec Gla-100	IVRS	26 weeks	NR§	✓	✓	✓	✓
	Meneghini, 201332	Asia, Europe, Israel, North America, Russia, South America, South Africa	OAD HbA1c 7–11%	685	Degludec (flexible) Degludec (once daily) Gla-100	IVRS	26 weeks	Degludec(flexible): 26/229 (11.4%) Degludec(once daily): 24/228 (10.5%) Gla-100: 27/230 (11.7%)	✓	✓	✓	✓
	Zinman, 201233	Europe, North America	Insulin naïve OAD HbA1c 7–10%	1023	Degludec Gla-100	IVRS	52 weeks	Degludec: 166/773 (21.5%) Glargine:60/257 (23.3%)	✓	✓	✓	✓
	Zinman (AM), 201334	Europe, Israel, North America, South Africa	Insulin naïve OAD HbA1c 7–10%	456	Degludec Gla-100	IVRS	26 weeks	Degludec: 38/230 (16.5%) Gla-100: 24/230 (10.4%)	✓	✓	✓
	Zinman (PM), 201334	Europe, North America	Insulin naïve OAD HbA1c 7–10%	467	Degludec Gla-100	IVRS	26 weeks	Degludec: 25/233 (10.7%) Gla-100: 25/234 (10.7%)	✓	✓	✓
Detemir vs Gla-100	Hollander, 200835	Europe and the USA	OAD and/or insulin HbA1c 7–11%	319	Detemir + aspart Gla-100 + aspart	TS	52 weeks	Detemir: 43/216 (19.9%) Gla-100: 23/107 (21.5%)	✓	✓	✓
	Meneghini, 201336	Asia, South America, USA	Insulin naïve OAD HbA1c 7–9%	453	Detemir Gla-100	NR	26 weeks	Detemir: 38/228 (16.7%) Gla-100: 41/229 (17.9%)	✓	✓	✓
	Raskin, 200937	NR	OAD and/or insulin HbA1c 7–11%	387	Detemir + aspart Gla-100 + aspart	NR	26 weeks	Detemir: 46/256 (18.0%) Gla-100: 18/131 (13.7%)	✓	✓	✓
	Rosenstock, 200838	Europe and the USA	Insulin naïve OAD HbA1c 7.5–10%	582	Detemir Gla-100	TS	52 weeks	Detemir: 60/291 (20.6%) Gla-100: 39/291 (13.4%)	✓	✓	✓
	Swinnen, 201039	Asia, Australia, Europe, Middle East (Turkey), North America, Russia, South America	Insulin naïve OAD HbA1c 7–10.5%	964	Detemir Gla-100	NR	24 weeks	Detemir: 10.1%§ Gla-100:4.6%§	✓	✓		✓
Detemir vs premixed	Holman, 200740	Europe	Insulin naïve OAD HbA1c 7–10%	708	Prandial insulin aspart Detemir Biphasic aspart 30	IVRS	52 weeks	Bolus: 17/239 (7.1%) Detemir: 10/234 (4.3%) Premixed insulin:13/235 (5.5%)	✓	✓
Detemir vs premixed	Liebl, 200941	Europe	OAD HbA1c 7–12%	715	Detemir + aspart Soluble aspart/protamine-crystallised aspart 30/70	Codes	26 weeks	Detemir: 44/541 (8.1%) Premixed insulin: 17/178 (9.6%)	✓	✓
Detemir vs NPH	Haak, 200542	Europe	HbA1c ≤12%	505	Detemir + aspart NPH + aspart	NR	26 weeks	Detemir: 26/341 (7.6%)§ NPH: 8/164 (4.9%)§	✓	✓
	Hermansen, 200643	Europe	Insulin naïve OAD HbA1c 7.5–10%	475	Detemir NPH	TS	24 weeks	Detemir: 4%§ NPH: 5%§	✓	✓	✓
	Montañana, 200844	Spain	On insulin± metformin HbA1c 7.5–11%	271	Detemir + aspart NPH + aspart	Codes	26 weeks	Detemir:7/126 (5.6%) NPH: 12/151 (7.9%)	✓	✓	✓
	Philis-Tsimakas, 200645	North America and Europe	Insulin naïve OAD HbA1c 7.5–11%	498	Detemir morning Detemir evening NPH	IVRS	20 weeks	Detemir (morning): 19/168 (11.3%) Detemir (evening): 16/170 (9.4%) NPH: 17/166 (10.2%)	✓		✓
	Raslová, 200446	8 Countries (not specified)	On insulin ±OADs HbA1c <12%	394	Detemir + insulin aspart NPH + human soluble insulin	NR	22 weeks	Detemir: 10/195 (5.1%)§ NPH: 6/199 (3.0%)§	✓	✓

All the studies were open-label, with the exception of Liebl et al1 (not reported).
*Safety population; exceptions: efficacy population for Buse et al,11 Raslová et al,46 Riddle et al,18 Tinahones et al22 and Vora et al.23
†Numerator for discontinuation rate=randomised patients−patients completing the study; denominator for discontinuation rate=randomised patients. Exceptions noted in footnote (§).
‡A=change in HbA1c, B=change in body weight, C=nocturnal hypoglycaemia rate, D=documented symptomatic hypoglycaemia rate.
§Exceptions to definition of discontinuation rate/or discontinuation rate not calculable with information available: Gough 2013 reported that 460 were randomised 1:1 (3 were randomised in error and were withdrawn, 1 withdrew consent (all prior to treatment)) and 228 and 229 received detemir and Gla-100, respectively, however, completion/withdrawal not described; Kazda et al15 reported ‘drop-out’ rates (however, numbers randomised to each group not provided and denominator may have been exposed rather than randomised patients); Swinnen et al's39 brief report does not make clear what the denominator was for completion rate provided (did not report number randomised to each group, only total randomised; did not report numbers of patients completing the study—only the percentages); Hermansen et al:43 denominator may be ITT population—475 were randomised but the breakdown between treatment arms is not clear; Haak et al,42 reported rates based on patients receiving treatment rather than randomised patients; Raslová et al46 reported rates reported based on ITT rather than randomised patients (ITT only 1 less than randomised, but number randomised to each treatment arm not provided in publication). In addition, Rosenstock et al28 reported data over 5 years; however, only the first year data were included in this NMA.
HbA1c, glycated haemoglobin; ITT, intention to treat; IVRS, interactive voice (or web) response system; NMA, network meta-analysis; NPH, neutral protamine Hagedorn;
NR, not reported; OAD,oral antidiabetic medication; T2DM, type 2 diabetes mellitus; TS, telephone system.