Simplifying complex treatment regimens in patients with type 2 diabetes mellitus (T2DM) improves treatment adherence and clinical outcomes while reducing the risk of adverse events and healthcare costs. |
Multiple clinical practice guidelines exist for T2DM treatment, but they often do not address the challenges of simplifying therapy in patients who have achieved therapeutic objectives but experience adverse events. |
The authors conducted a literature review to evaluate the evidence and propose a strategy to simplify complex antidiabetic treatments in patients with T2DM. |
Patient selection criteria for simplified treatment regimens may include assessing beta cell reserve and considering insulin doses to achieve reasonable metabolic control without compromising glycemic outcomes. |
Introduction
Methods
Literature Review
Evaluation of the Evidence
Characteristics of the Evidence
Study | Design | Key inclusion criteria | Key exclusion criteria | n | Duration (months) |
---|---|---|---|---|---|
Ramírez-Rincón, Colombia (2022) [42] | Multicenter, retrospective, cohort study | T2DM treated with IdegLira | Pregnant women, liver insufficiency, chronic kidney disease | 64 | 3–7 |
REX study, Italy (2022) [57] | Multicenter, prospective, cohort study | Age 18 years or more, T2D diagnosed at least 12 months before enrolment | Type 1 diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes in adults, gestational diabetes, or any hyperglycemic state other than T2D | 331 | 18 |
BEYOND trial, Naples, Italy (2021) [12] | Randomized, pragmatic, parallel-group, active-control, open-label, single-center, clinical trial | Age > 35 years, HbA1c > 7.5% (58 mmol/mol), and current use of a full BBI regimen (four injections daily) | History of diabetic ketoacidosis or pancreatitis, impaired kidney function liver insufficiency | 305 102 assigned to IdegLira or LixiLan | 6 |
Persano et al., Treviso, Italy (2021) [13] | Single-center, prospective, cohort study | Age > 18 years, C-peptide > 1 ng/ml | Type 1 DM, age > 75 years, patients naïve to insulin, pregnant women, diabetic kidney disease and glomerular filtration rate < 15 ml/min, chronic heart failure (New York Heart Association class III–IV), thyroid disease, known hepatic disease, personal or family history of medullary thyroid carcinoma, patients with multiple endocrine neoplasia syndrome type 2 or a history of pancreatitis | 45 | |
Zenari et al., Italy (seven diabetes centers) (2021) [14] | Multicenter, retrospective, cohort study | IDegLira therapy following the switch from prior treatments | Age < 18 years; insulin naive; concomitant or suspected malignant diseases, recent acute diseases, severe renal failure (glomerular filtration rate 15 mL/min) severe liver failure, congestive heart failure (New York Heart Association functional class IV), a high degree of fragility, chronic pancreatitis | 244 | 12 |
Di Loreto et al., Perugia, Italy (2020) [7] | Single-center, retrospective, cohort study | Age > 18 years, unsatisfactory glycemic control for either hypoglycemic episodes or weight gain | Personal or family history of medullary thyroid carcinoma, or history of pancreatitis or insulin-naïve subjects | 137 | 18 |
Taybani et al., Hungary (2019) [5] | Prospective, single-arm clinical trial | Age ≥ 18 years, random serum C-peptide levels > 1.1 ng/mL, HbA1c ≤ 7.5%, insulin DID < 70 IU/day and DID < 0.6 IU/kg/day | Type 1 diabetes, active cancer, anemia, and acute or chronic kidney disease | 69 | 3 |
The EXTRA study, Germany, Switzerland, UK, Austria, and Sweden (2018) [3] | Multicenter, retrospective, cohort study | All patients who received at least one prescription of IDegLira | None | 611 566 provided complete follow-up data | 6 |
Sofra, Switzerland (2017) [2] | Single-center, prospective, cohort study | Poor glycemic control, (HbA1c greater than 8.0%), more than two oral antidiabetic medications and more than one injection daily, or if the patient would benefit from the addition of the liraglutide component of IDegLira for weight management | None | 61 5 early discontinuation | 6 |
Study | Baseline treatment | Daily insulin dose | Treatment transition scheme | IdegLira starting dose | IdegLira tiitration scheme | Main outcomes |
---|---|---|---|---|---|---|
Ramírez-Rincón, Colombia (2022) [42] | Basal insulin with or without simultaneous treatment with one or more AD or rapid insulin | 38 (IQR 30.5) units | Stop all insulin injections and started a single daily injection of IDegLira | As recommended by the manufacturer | As suggested by the manufacturer | HbA1c change − 1.05 (CI 95% − 1.45 to − 0.65) DID change − 10 (CI 95% − 17 to − 2.5) units Weight change 0.5 (− 0.25 to 1.3) kg |
REX study, Italy (2022) [57] | Basal insulin with or without simultaneous treatment with one or more AD or rapid insulin | Basal insulin 15.0 (IQR 10.0–20.0) Basal + bolus 42.0 (IQR 30.0–52.0) | NR | Basal insulin 16 (IQR 16 to 20) dose steps Basal + bolus 16 (15 to 20) dose steps | NR | Interim analysis no report of the main result at the moment of the search |
BEYOND trial, Naples, Italy (2021) [12] | MDI (four injections daily) with or without metformin | NR | Stop all insulin injections and started a single daily injection of IDegLira | As recommended by the manufacturer | As suggested by the manufacturer | HbA1c change − 0.6 ± 0.8% DID change − 27.1 ± 14.2 units Weight change − 1.9 ± 4.3 DTSQ change 34.2 ± 3.7 |
Persano et al., Treviso, Italy (2021) [13] | MDI (four injections daily) with or without metformin | 42 (IQR 30–59) units | Stop all insulin injections and started a single daily injection of IDegLira | 16 dose steps | Twice weekly to reach a 90–130 mg/dl fasting glycemic target (130–160 mg/dl for weak elderly patients); adjustments were in increments of 2 dose steps at a time | HbA1c change − 0.67% Weight change − 2.4 ± 4.3 kg DTSQ change 7.5 |
Zenari et al., Italy (seven diabetes centers) (2021) [14] | Basal insulin with or without simultaneous treatment with one or more AD or rapid insulin | Basal insulin 21.1 ± 9.8 IU Basal + bolus 55.9 ± 26.3 IU | At the discretion of the treating physician | Basal insulin 18.7 ± 6.8 dose steps Basal + bolus 20.2 ± 7.6 dose steps | At the discretion of the treating physician | Basal HbA1c change − 1.1 ± 1.3% DID change 2.8 ± 13.4 units Weight change − 1.1 ± 4.9 kg at 6 months Basal + bolus HbA1c change − 0.2 ± 1.2% DID change − 31.6 ± 25.1 units Weight change − 2.8 ± 5.4 kg at 6 months |
Di Loreto et al., Perugia, Italy (2020) [7] | Basal insulin with or without simultaneous treatment with one or more antidiabetic drug (AD) or rapid insulin | Basal insulin 0.29 (0.2) IU/kg Basal + bolus 0.62 (0.33) IU/kg | NR | NR | At the discretion of the treating physician | Basal HbA1c change − 0.9 ± 1.0% DID change 8.9 ± 9.3 units Basal + GLP1RA HbA1c change − 1.2 ± 0.4% DID change 0.3 ± 9.0 units Basal + bolus HbA1c change − 1.2 ± 1.1% DID change − 38 ± 2.8 units |
Taybani et al., Hungary (2019) [5] | MDI (four injections daily) with or without metformin | 43.31 (IQR 10.99) units | Stop all insulin injections and started a single daily injection of IDegLira | 16 dose steps | NR | HbA1c change − 0.30 (CI 95% − 0.42 to − 0.18) DID change − 22.55 (CI 95% − 24.96 to − 20.14) units Weight change − 3.11 (CI 95% − 4.04 to − 2.18) kg Insulin requirement − 0.24 (CI 95% − 0.27 to − 0.21) IU/kg |
The EXTRA study, Germany, Switzerland, UK, Austria, and Sweden (2018) [3] | AD with or without insulin 115 patients treated with basal insulin + AD, 145 with insulin + GLPRA and AD, and 161 patients treated with MDI and AD | Basal + AD 31.4 ± 21.1 units Basal + ARGLP1 44.2 ± 33.9 units MDI + AD 67.7 ± 42.5 | NR | The majority (83.7%) of patients initiated on between 10 and 30 dose steps | Basal + AD Mean 8.5 dose steps at 6 months Basal + ARGLP1 Mean 6.5 dose steps at 6 months MDI + AD Mean 8.5 dose steps at 6 months | Basal + AD HbA1c change − 0.9% DID change − 1.7 units Weight change − 0.1 kg Basal + GLP1RA HbA1c change − 0.6% DID change − 2.5 units Weight change − 0.2 kg MDI + AD HbA1c change − 0.7% DID change − 20.7 units Weight change − 2.4 kg |
Sofra, Switzerland (2017) [2] | Basal insulin with or without simultaneous treatment with one or more AD or rapid insulin | Stop all insulin injections and started a single daily injection of IdegLira In patients treated with 50 or more insulin units, a transition phase was included with the addition of a slow-acting insulin during titration of IDegLira | 20 dose steps in insulin-treated patients and 16 dose steps in insulin-naïve patients | Four dose steps once weekly, according to individualized fasting blood glucose targets | HbA1c change − 1.7% DID change − 14.6 units Weight change − 1.9 kg |