Clinical study | Patient population | Basal-plus dosage Intervention | Comparator | Primary endpoint | Key outcomes |
B+ combination: IGlar + IGlu | |||||
OPAL8
Open-label RCT; 24-week FU | Outpatient; T2D; age ≥18 years; HbA1c >6.5%–9.0%; FBG ≤6.7 mmol/L; IGlar + OADs for ≥3 months | B+ (breakfast): IGlar + OADs + IGlu before breakfast (n=162) | B+ (main meal): IGlar + OADs + IGlu before main meal of the day (n=154) | Change in HbA1c from baseline to endpoint |
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Davidson et al
9
Open-label RCT; 24-week FU | Outpatient; T2DM ≥6 months, age 18–79 years, HbA1c ≥8%, stable dose of 2–3 OADs |
B+ 1: IGlar + OADs + IGlu before the largest meal of the day (n=101) B+ 2: IGlar + OAD + IGlu before the two largest meals of the day (n=102) | BB: IGlar +OADs + IGlu before all three meals (n=100) | Change in HbA1c from randomization to study end (week 24) |
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POC21
Open-label RCT; 6-month FU | Outpatient; T2D; age 18–75 years; BMI 25–45 kg/m2; HbA1c 7.5%–9.5%; treatment with basal insulin + Met ≥1 g/day for >3 months | B+ : IGlar + OADs + IGlu before main meal of the day (n=45) | BOT: IGlar + OADs only (n=51) | Proportion of patients achieving HbA1c <7% at endpoint |
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Choe et al
13
Retrospective chart review; 6-month FU | Outpatient; T2D; in Severance Hospital Diabetes Insulin Education Registry; IGlar ≥6 months; recent addition of IGlu 1×/day | B+ : IGlar + IGlu 1×/day (n=87) | n.a. | Changes in glycemic and clinical parameters |
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ELEONOR15
Open-label RCT; 24-week FU | Outpatient; T2DM ≥12 months; age 30–70 years; BMI>25 kg/m2; HbA1c 7.5%–11%; maximum dose OADs for ≥3 months | B+ (telecare): IGlar + Met 1 g 2×/day + IGlu 1×/day at dinner time with telecare monitoring (n=115) | B+ (SMBG): IGlar + Met 1 g 2×/day + IGlu 1×/day at dinner time with SMBG (n=126) | Change in HbA1c from baseline to end of treatment phase |
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OSIRIS20
Open-label RCT; 12-month FU | Outpatient; T2D; age 18–75 years; BMI ≤40 kg/m2; HbA1c >7%; treated with basal insulin and ≥2 OADs |
B+
: IGlar + Met + IGlu before main meal; subsequent stepwise addition of IGlu (n=165) B+ (+IS): IGlar + Met + insulin secretagogue + IGlu before main meal; subsequent stepwise addition of IGlu (n=100) | BB: IGlar + IGlu 3×/day before meals + Met (n=120) | To show non-inferiority in terms of efficacy between the treatment arms as measured by HbA1c |
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Umpierrez et al
18 19
Open-label RCT; 8-day FU | Inpatient; hospitalized, non-ICU, general medicine and surgery patients; T2DM >3 months; age 18–80 years; FBG 140–400 mg/dL; preadmission management with diet, OADs or daily insulin ≤0.4 U/kg | B+ : IGlar + corrective IGlu before meals and at bedtime only when BG >140 mg/dL (n=133) |
BB: IGlar + IGlu before all meals + corrective IGlu when BG >140 mg/dL (n=144) SSI: Sliding scale regular insulin when BG >140 mg/dL (n=74) | Difference in glycemic control, as measured by daily BG concentrations |
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All To Target16
Open-label RCT; 60-week FU | Outpatient; T2D; age 30–80 years; BMI <45 kg/m2; HbA1c >7.5%; 2–3 OADs for ≥3 months; <1 week insulin use in past 12 months |
Basal+
1: IGlar + IGlu 1×/day with main meal; ±OADs (n=194) Basal+ ≤ 3: IGlar + IGlu up to 3×/day; ±OADs (n=194) | Premix: IAsp/IAsp protamine 30/70 2×/day at breakfast and dinner time; ±OADs (n=194) | Non-inferiority of treatment options based on the reduction of HbA1c from baseline to week 60 |
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LanScape23
Open-label RCT; 24-week FU | Outpatient; T2D; aged 18–75 years; HbA1c ≥7.5% and ≤11%; BMI ≤40 kg/m2; basal insulin for ≥3 months; no prior GLP-1 RA, DPP-4i, biphasic, short-acting or rapid-acting insulin | B+ : IGlar + IGlu with largest meal; no OADs (except Met) (n=170) | Premix: IAsp/IAsp protamine 30/70 2×/day at breakfast and dinner time; no OADs (except Met) (n=165) | Change in HbA1c |
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Jin et al
22
Open-label RCT; 24-week FU | Outpatient; T2D; age ≥20 years; BMI <30 kg/m2; HbA1c 7.0%–10.0%; FPG <130 mg/dL; IGlar ≥12 weeks | B+: IGlar + IGlu before largest meal for 12 weeks; subsequently, second IGlu bolus before second largest meal, where HbA1c> 7.0%; ±OADs (n=78) | Premix: IAsp/IAsp protamine 30/70 before breakfast and dinner;±OAD (n=82) | Change in HbA1c after 24 weeks |
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GetGoal Duo-224
Open-label RCT; 26-week FU | Outpatient; T2DM ≥1 year; BMI >20 and <40 kg/m2; basal insulin for ≥6 months; HbA1c ≥7% and ≤9%; FBG ≤140 mg/dL; ≤3 OADs |
B+
: IGlar + IGlu before main meal; ±Met (n=298) BB: IGlar + IGlu 3×/day before meals; ±Met (n=295) | Lixisenatide: IGlar + lixisenatide 20 mg before main meal; ±Met (n=297) | HbA1c reduction with the treatment options |
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B+ combination: IGlar + ILis | |||||
Tinahones et al
26
Open-label RCT; 24-week FU | Outpatient; T2D; age ≥18 and ≤75 years; BMI ≤45 kg/m2; HbA1c ≥7.5% and ≤10.5%; FPG ≤6.7 mmol/L; Met≥ 1500 mg/day for ≥8 weeks and/or pioglitazone ≥30 mg/day for ≥12 weeks; IGlar for ≥90 days | B+ : Bedtime IGlar+ ILis before largest meal; +Met/pioglitazone (n=240) | Premix: LM25 before breakfast and dinner; +Met/pioglitazone (n=236) | Change in HbA1c after 24 weeks |
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Gracia-Ramos et al
25
Open-label RCT; follow-up during hospital stay | Inpatient; hospitalized, non-ICU patients; T2DM >3 months; BG >140 and <400 mg/dL on admission; treatment with diet, OADs or low-dose insulin (≤0.4 U/kg) before admission; consumption of ≥75% of indicated diet | B+ : IGla + ILis before meals when BG >140 mg/dL; no OADs (n=25) | Premix: LM75/25 + ILis before meals when BG >140 mg/dL; no OADs (n=25) | To compare the safety and efficacy of the study treatments |
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Gross et al
14
Post hoc analysis of Tinahones et al 26; 24-week FU | Outpatient; T2D; age ≥18 and ≤75 years; BMI ≤45 kg/m2; HbA1c ≥7.5 and ≤10.5%; FPG ≤6.7 mmol/L; Met ≥1500 mg/day for ≥8 weeks and/or pioglitazone ≥30 mg/day for ≥12 weeks; IGlar for ≥90 days |
B+
: Bedtime IGlar+ ILis before main meal; +Met/pioglitazone Main meal timing: breakfast (n=40); lunchtime (n=107); evening (n=93) |
Premix: LM25 before breakfast and dinner; +Met/pioglitazone. Main meal timing: breakfast (n=51); lunchtime (n=71); evening (n=114) | To compare the safety and efficacy of the study treatments |
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B+ combination: IDet + IAsp | |||||
STEPWise28
Open-label RCT; 48-week FU | Outpatient; T2DM ≥6 months; age ≥18 years; HbA1c 7.5%–10%; receiving basal insulin +1–3 OADs | B+ (simpleSTEP): IDet + OAD + stepwise addition of IAsp at largest meal based on premeal glucose (n=150) | B+ (ExtraSTEP): IDet + OAD + stepwise addition of IAsp at meal with largest prandial glucose increment based on postmeal glucose (n=146) | Change in HbA1c levels at 36 weeks after randomization |
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FullSTEP27
Open-label RCT; 32-week FU | Outpatient; T2DM ≥12 months; age ≥18 years; HbA1c 7%–9%; BMI <40.0 kg/m²; NPH, IGlar or IDet for ≥6 months | B+ : IDet + IAsp before largest meal for 11 weeks; subsequent stepwise addition of IAsp up to 3×/day; ±OADs (n=201) | BB: IDet + prandial IAsp 3×/day; ±OADs (n=200) | Change in HbA1C from baseline to week 32 |
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LM25: insulin lispro protamine suspension 75% and insulin lispro solution 25%; B+, basal plus; BB, basal-bolus; BG, blood glucose;BMI, body mass index; BOT, basal-supported oral therapy; FBG, fasting blood glucose; FU, follow-up; GI, gastrointestinal;GLP-1 RA, glucagon-like peptide-1 receptor agonist; IAsp, insulin aspart; IDet, insulin detemir; IGlar, insulin glargine; IGlu, insulin glulisine; ILis, insulin lispro;LOS, length of stay; Met, metformin;n.a., not applicable; OAD, oral antidiabetic drug; PPBG, postprandial blood glucose; RCT, randomized controlled trial; SMBG, self-monitored blood glucose; T2D, type 2 diabetes.