Empagliflozin in combination with oral agents in young and overweight/obese Type 2 diabetes mellitus patients: A pooled analysis of three randomized trials
Abstract
Aims This analysis aimed to evaluate efficacy and safety of empagliflozin in combination therapy in <65 y.o. patients, overweight/obese, and with uncontrolled T2DM.Methods Pooled analysis from three phase-III trials, in <65 y.o. patients, with BMI 25-35kg/m 2, and HbA1c ≥8% at baseline. Patients (N=439) were randomized to placebo (n=138), empagliflozin 10mg (n=160), or empagliflozin 25mg (n=141) once daily (24weeks) as add-on to metformin, to metformin plus sulfonylurea, or to pioglitazone ± metformin.Results At week 24, adjusted mean (SE) changes from baseline in HbA1c were -0.19% (0.07) for placebo vs. -1.10% (0.07) and -1.10% (0.07) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adjusted mean (SE) changes from baseline in weight were -0.33kg (0.21) for placebo vs. -1.94kg (0.19) and -2.14kg (0.20) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adverse events were reported in 57.2% on placebo, 64.4% on empagliflozin 10mg and 59.6% on empagliflozin 25mg. Genital infection AEs were reported in 1.4% on placebo, 3.8% on empagliflozin 10mg, and 5.0% on empagliflozin 25mg.Conclusions In this specific population, empagliflozin in combination with other oral agents, significantly reduced HbA1c and body weight and was well tolerated.
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Previous RCTs reported that selective SGLT2 inhibitors reduce body weight by 1-3 kg in diabetic patients with and without obesity.
“Previous RCTs reported that selective SGLT2 inhibitors, a new class of anti-diabetes drugs, have been shown to reduce body weight (1–3 kg reduction) in diabetic patients with and without obesity [99–102].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [100]
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“88% Empagliflozin 10 mg, 25 mg Placebo Sitagliptin 76 weeks Deaths, CV events Romera (47) T2DM and”
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“Romera et al.[26] EMPA + MET, EMPA + SU, EMPA + TZD 439 Placebo + MET, placebo + SU, placebo + TZD ↓ up to 1.”
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“The efficacy, safety, and tolerability profile of empagliflozin and dapagliflozin as an add-on therapy were investigated in various clinical studies that yielded similar results to our study [18-26].”
ResultAn Overview of Prospective Drugs for Type 1 and Type 2 Diabetes
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“105,106 Subgroup analysis of a systematic review conducted by Xu et al. 107 (15 studies) in 2022 reported that compared with placebo, dapagliflozin combined with metformin [mean difference (MD) = −0.45, 95% CI: −0.61 to 0.29, p < 0.00001], insulin (MD = −0.59, 95% CI: −0.83 to −0.36, p < 0.00001),…”
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- Authors
- Romera, I., Gomis, R., Crowe, S., de Pablos-Velasco, P., Aranda, U., García, A., Kis, S. G., & Naderali, E.
- Affiliations
- Eli Lilly (Spain) (ES)
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim (Spain) (ES)
- Eli Lilly (United Kingdom) (GB)
- Corresponding author
- Romera, Irene
- ORCID
- Romera, Irene
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 30
- Issue
- 8
- Pages
- 1571-1576
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- OpenAlex
- W2498155300
- Cited by
- 9
- References
- 22
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- Hope's Institutional Research Archive (Liverpool Hope University) (acceptedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- empagliflozin, type 2 diabetes, combination therapy, metformin, sulfonylureas, pioglitazone, glycemic control, HbA1c, weight loss, young adults, overweight and obesity, adverse events, genital tract infection, SGLT2 inhibitors
- MeSH terms
- Benzhydryl Compounds, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Female, Glucosides, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Obesity, Treatment Outcome, Overweight
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