Table 1.
Major Characteristics of the Included Randomized Controlled Trials and Participants
| RCT ID | Study place | Characteristics of study subjects | Study arms | No. | Age, yr | Male, % | Duration of T2DM, yr | Baseline HbA1c, % | Study duration, wk |
|---|---|---|---|---|---|---|---|---|---|
| Chacra et al. (2017) [6] | Multi-country, multicenter | eGFR <60 mL/min/1.73 m2 or ESRD | Omarigliptin 12.5/25 mg | 106 | 65.9±9.4 | 63.6 | 14.9±8.2 | 8.3±0.8 | Phase A: 24a |
| On no, single, or combination AHA or stable dose of insulin with HbA1c ≥ 6.5%–≤10.0% | Placebo | 106 | 64.5±9.7 | 59.4 | 15.1±8.7 | 8.3±0.8 | Phase B: 30 | ||
| Pre-randomization FPG <7.22–<14.43 mmol/L | |||||||||
| Gantz et al. (2017a) [7] | Multicenter in Japan | On stable dose of an SU, GL, BG, TZD, or AGI | Omarigliptin 25 mg+Background OADs | 389 | 61±10 | 69.7 | 9.3±5.8 | 8.0±0.7 | Phase A: 24a |
| Pre-randomization HbA1c 7.0%–10.0% | Placebo+Background OADs | 196 | 61±11 | 74.0 | 9.7±5.7 | 8.0±0.7 | Phase B: 28 | ||
| Gantz et al. (2017b) [8] | Multicenter in Japan | Treatment-naïve or on AHA | Omarigliptin 25 mg | 166 | 60±11 | 62.7 | 7.4±5.5 | 7.9±0.7 | Phase A: 24a |
| Pre-randomization HbA1c 7.0%–10.0% | Sitagliptin 50 mg | 164 | 60±9 | 69.7 | 7.4±5.3 | 8.0±0.8 | Phase B: 28 | ||
| Placebo | 82 | 61±9 | 68.7 | 8.6±5.1 | 8.1±0.7 | ||||
| Gantz et al. (2017c) [9] | Multi-country, multicenter | Established CVD | Omarigliptin 25 mg | 2,092 | 63.7±8.5 | 69.6 | 12.0±7.6 | 8.0±0.9 | 142 (with an 18-week period of unadjusted background medicationa) |
| Stable diabetes treatment regimens for at least 12 weeks | |||||||||
| Pre-randomization HbA1c 6.5%–10.0% | |||||||||
| Placebo | 2,100 | 63.6±8.5 | 70.7 | 12.1±8.0 | 8.0±0.9 | ||||
| Gantz et al. (2017d) [10] | Multi-country, multicenter | Drug-naïve or not on an AHA for ≥12 weeks | Omarigliptin 25 mg | 102 | 38.8±4.7 | 65.7 | 2.9±2.2 | 7.9±0.8 | 24 |
| HbA1c 7.0%–10.0% at screening and FPG >7.2–<14.4 mmol/L at randomization | Placebo | 101 | 39.5±4.5 | 59.4 | 3.3±3.0 | 8.1±0.9 | |||
| Goldenberg et al. (2017) [11] | Multi-country, multicenter | On a stable dose of metformin (≥1.5 g) for ≥12 weeks | Omarigliptin 25 mg+Metformin | 322 | 57±10 | 46.9 | 7.0±4.5 | 7.5±0.8 | 24 |
| HbA1c ≥6.5%–≤9.0% at screening and FPG >7.2–<14.4 mmol/L at randomization | Sitagliptin 100 mg+ Metformin | 320 | 58±10 | 54.7 | 7.5±5.6 | 7.5±0.7 | |||
| Handelsman et al. (2017) [12] | Multi-country, multicenter | On a stable dose of metformin (≥1.5 g) for ≥12 weeks | Omarigliptin 25 mg+ Metformin | 375 | 58±10 | 54.0 | 7.6±5.1 | 7.5±0.8 | 54 |
| HbA1c ≥6.5%–≤9.0% at screening and FPG >7.0–<14.4 mmol/L at randomization | Glimepiride+Metformin | 375 | 58±9 | 56.3 | 7.7±4.9 | 7.4±0.7 | |||
| Hattori (2020) [13] | Single-center in Japan | Attended the study center for at least 12 months | Omarigliptin 25 mg | 56 | 59.00±7.33 | 71 | Not available | 6.91±0.77 | 52 |
| HbA1c >6.0% regardless of diet, exercise, and daily medications with the DDP-4 inhibitors sitagliptin (50 mg) or linagliptin (5 mg) | Sitagliptin 50 mg or linagliptin 5 mg | 28 | 59.17±7.85 | 75 | Not available | 6.85±0.75 | |||
| Home et al. (2018) [14] | Multi-country, multicenter | At screening were either not on an OGLD for at least 12 weeks and had a screening visit HbA1c ≥7.0% and ≤10.0% on diet and exercise alone, or had HbA1c ≥6.5% and ≤9.0% on OGLD monotherapy or low-dose (50% of maximum label dose of each agent) dual oral therapy | Omarigliptin 25 mg | 165 | 57.4±9.2 | 57.6 | 5.4±3.8 | 8.0±0.9 | Phase A: 24a |
| Placebo | 164 | 57.0±9.7 | 59.1 | 5.7±4.7 | 8.1±1.0 | Phase B: 30 | |||
| Ishii et al. (2023) [15] | Multicenter in Japan | Used once- or twice-daily DPP-4 inhibitors | Omarigliptin 25 mg | 106 | 65.3±11.8 | 50.9 | Not available | 6.8±0.6 | 12 |
| Did not change the anti-diabetic agents (dose, usage, or type) within 8 weeks before giving their consent | Once or twice-daily DPP-4 inhibitors | 106 | 65.1±11.7 | 48.1 | Not available | 6.9±0.7 | |||
| HbA1c <10.0% upon giving consent | |||||||||
| Omarigliptin 25 mg | 123 | 61.1±11.0 | 69.9 | 12.6±9.0 | 8.8±0.7 | Phase A: 16a | |||
| Kadowaki et al (2021) [16] | Multicenter in Japan | At screening, either on a stable regimen of insulin ± a single OHA with an HbA1c of ≥7.0% and ≤10.0% | Placebo | 61 | 60.9±11.7 | 77.0 | 13.8±7.8 | 8.8±0.8 | Phase B: 36 |
| 2 weeks before randomization, HbA1c of ≥7.5% and ≤10.0%, as well as FPG of ≥7.0 and ≤12.8 mmol/L | |||||||||
| Lee et al. (2017) [17] | Multi-country, multicenter | On dual combination therapy with metformin ≥1.5 g/day for ≥12 weeks and either glimepiride or another sulfonylurea | Omarigliptin 25 mg+Metformin+Sus | 153 | 57.2±8.4 | 47.4 | 9.8±5.3 | 8.5±0.8 | 24 |
| HbA1c ≥7.5% and ≤10.5% | Placebo+Metformin+SUs | 153 | 58.4±9.4 | 48.4 | 10.4±5.5 | 8.6±0.8 | |||
| Ohara et al. (2021) [18] | Multicenter in Japan | Treatment with daily DPP-4 inhibitors for ≥12 weeks | Omarigliptin 25 mg | 18 | 66.8±6.6 | 72.2 | 11.9±7.6 | 7.2±0.4 | 24 |
| HbA1c ≥6.5% | Daily DPP-4 inhibitorsb | 18 | 69.0±9.2 | 66.7 | 14.5±6.5 | 7.2±0.4 | |||
| Shankar et al. (2017) [19] | Multi-country, multicenter | On a stable dose of metformin monotherapy (≥1.5 g/day) for at least 12 weeks | Omarigliptin 25 mg+Metformin | 201 | 57.5±8.1 | 50.2 | 8.2±5.2 | 8.1±0.9 | Phase A: 24a |
| HbA1c of 7.0%–10.5% at screening | Placebo+Metformin | 201 | 56.8±9.1 | 50.7 | 7.4±5.6 | 8.0±0.9 | Phase B: 80 | ||
| Sheu et al. (2015) [20] | Multi-country, multicenter | Not on an oral AHA (off AHA medication for ≥14 weeks) | Omarigliptin 25 mg | 114 | 55.1±8.8 | 60.5 | 5.9±5.2 | 8.1±1.0 | Phase A: 12a |
| HbA1c ≥7.0% and ≤10.0% | Placebo | 113 | 55.9±8.4 | 57.0 | 5.8±4.6 | 8.1±0.9 | Phase B: 66 | ||
| Yoshizawa et al. (2021) [21] | Multicenter in Japan | On maintenance hemodialysis for >6 months | Omarigliptin 12.5 mg | 14 | 67.7±8.9 | 85.7 | 16.0±8.7 | 6.2±0.9 | 24 |
| Using DPP-4 inhibitors for more than 3 months | Linagliptin 5 mg | 16 | 67.5±9.0 | 75.0 | 20.8±11.3 | 6.5±1.0 | |||
| HbA1c <9.0% |
RCT, randomized controlled trial; T2DM, type 2 diabetes mellitus; HbA1c, hemoglobin A1c; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; AHA, antihyperglycemic agent; FPG, fasting plasma glucose; SU, sulphonylureas; GL, glinides; BG, biguanides; TZD, thiazolidinediones; AGI, alpha-glucosidase inhibitors; OAD, oral anti-diabetic drug; CVD, cardiovascular disease; DDP-4, dipeptidyl peptidase-4; OGLD, oral glucose-lowering drug; OHA, oral hypoglycemic agent.
a
Included in the meta-analysis;
b
Sitagliptin 50 mg/day, linagliptin 5 mg/day, alogliptin 25 mg/day, vildagliptin 100 mg/day, saxagliptin 5 mg/day, teneligliptin 20 mg/day.