Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis
Background: There are multiple glucose-lowering drugs available as alternative initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin. However, little comparative and systematic data are available for them as initial monotherapy. This study estimated and...
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MDPI AG
2022-11-01
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| Series: | Journal of Clinical Medicine |
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| author | Shuyan Gu Xiaoqian Hu Lizheng Shi Xuemei Zhen Xueshan Sun Minzhuo Huang Yuxuan Gu Hengjin Dong |
| author_facet | Shuyan Gu Xiaoqian Hu Lizheng Shi Xuemei Zhen Xueshan Sun Minzhuo Huang Yuxuan Gu Hengjin Dong |
| author_sort | Shuyan Gu |
| collection | DOAJ |
| description | Background: There are multiple glucose-lowering drugs available as alternative initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin. However, little comparative and systematic data are available for them as initial monotherapy. This study estimated and compared the treatment effects of glucose-lowering drugs as initial monotherapy for type 2 diabetes. Methods: PubMed, Web of Science, Embase, CNKI, Chongqing VIP, and WanFang Data from 1 January 1990 until 31 December 2020 were searched for randomized controlled trials which compared a glucose-lowering drug with placebo/lifestyle-intervention for type 2 diabetes. Drug classes included metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), glinides (NIDEs), α-glucosidase inhibitors (AGIs), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), insulins (INSs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs). Results: A total of 185 trials were included, identifying 38,376 patients from 56 countries across six continents. When choosing an initial drug monotherapy alternative to metformin, SUs were most efficacious in reducing HbA1c (−1.39%; 95% CI −1.63, −1.16) and FPG (−2.70 mmol/L; 95% CI −3.18, −2.23), but increased hypoglycemia risks (5.44; 95% CI 2.11, 14.02). GLP-1RAs were most efficacious in reducing BMI (−1.05 kg/m<sup>2</sup>; 95% CI −1.81, −0.29) and TC (−0.42 mmol/L; 95% CI −0.61, −0.22). TZDs were most efficacious in increasing HDL-C (0.12 mmol/L; 95% CI 0.07, 0.17). SGLT2is were most efficacious in lowering SBP (−4.18 mmHg; 95% CI −4.84, −3.53). While AGIs conferred higher risk of AE-induced discontinuations (2.57; 95% CI 1.64, 4.03). Overall, only GLP-1RAs showed an integrated beneficial effect on all outcomes. Our results also confirmed the intraclass differences in treatment effects across drugs. Most trials were short-term, and no significant differences in mortality, total vascular events, myocardial infarction, heart failure, stroke, or diabetic nephropathy were observed across drug classes. Conclusions: Our results suggest a potential treatment hierarchy for decision-makers, with GLP-1RAs being the preferred alternative therapy to metformin regarding their favorable efficacy and safety profiles. |
| first_indexed | 2024-03-09T17:43:53Z |
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| spelling | doaj.art-b70ae9172c3b43088bf4ecd2e41363912023-11-24T11:22:49ZengMDPI AGJournal of Clinical Medicine2077-03832022-11-011123709410.3390/jcm11237094Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-AnalysisShuyan Gu0Xiaoqian Hu1Lizheng Shi2Xuemei Zhen3Xueshan Sun4Minzhuo Huang5Yuxuan Gu6Hengjin Dong7Center for Health Policy and Management Studies, School of Government, Nanjing University, Nanjing 210023, ChinaCollege of Politics and Public Administration, Qingdao University, Qingdao 266071, ChinaDepartment of Global Health Management and Policy, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USACentre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine (NHC Key Laboratory of Health Economics and Policy Research), Shandong University, Jinan 250012, ChinaCenter for Health Policy Studies, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaCenter for Health Policy Studies, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaCenter for Health Policy Studies, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaCenter for Health Policy Studies, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaBackground: There are multiple glucose-lowering drugs available as alternative initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin. However, little comparative and systematic data are available for them as initial monotherapy. This study estimated and compared the treatment effects of glucose-lowering drugs as initial monotherapy for type 2 diabetes. Methods: PubMed, Web of Science, Embase, CNKI, Chongqing VIP, and WanFang Data from 1 January 1990 until 31 December 2020 were searched for randomized controlled trials which compared a glucose-lowering drug with placebo/lifestyle-intervention for type 2 diabetes. Drug classes included metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), glinides (NIDEs), α-glucosidase inhibitors (AGIs), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), insulins (INSs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs). Results: A total of 185 trials were included, identifying 38,376 patients from 56 countries across six continents. When choosing an initial drug monotherapy alternative to metformin, SUs were most efficacious in reducing HbA1c (−1.39%; 95% CI −1.63, −1.16) and FPG (−2.70 mmol/L; 95% CI −3.18, −2.23), but increased hypoglycemia risks (5.44; 95% CI 2.11, 14.02). GLP-1RAs were most efficacious in reducing BMI (−1.05 kg/m<sup>2</sup>; 95% CI −1.81, −0.29) and TC (−0.42 mmol/L; 95% CI −0.61, −0.22). TZDs were most efficacious in increasing HDL-C (0.12 mmol/L; 95% CI 0.07, 0.17). SGLT2is were most efficacious in lowering SBP (−4.18 mmHg; 95% CI −4.84, −3.53). While AGIs conferred higher risk of AE-induced discontinuations (2.57; 95% CI 1.64, 4.03). Overall, only GLP-1RAs showed an integrated beneficial effect on all outcomes. Our results also confirmed the intraclass differences in treatment effects across drugs. Most trials were short-term, and no significant differences in mortality, total vascular events, myocardial infarction, heart failure, stroke, or diabetic nephropathy were observed across drug classes. Conclusions: Our results suggest a potential treatment hierarchy for decision-makers, with GLP-1RAs being the preferred alternative therapy to metformin regarding their favorable efficacy and safety profiles.https://www.mdpi.com/2077-0383/11/23/7094type 2 diabetesinitial monotherapymetforminsulfonylureasthiazolidinedionesglinides |
| spellingShingle | Shuyan Gu Xiaoqian Hu Lizheng Shi Xuemei Zhen Xueshan Sun Minzhuo Huang Yuxuan Gu Hengjin Dong Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis Journal of Clinical Medicine type 2 diabetes initial monotherapy metformin sulfonylureas thiazolidinediones glinides |
| title | Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis |
| title_full | Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis |
| title_fullStr | Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis |
| title_short | Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis |
| title_sort | choice of glucose lowering drugs as initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin a systematic review and meta analysis |
| topic | type 2 diabetes initial monotherapy metformin sulfonylureas thiazolidinediones glinides |
| url | https://www.mdpi.com/2077-0383/11/23/7094 |
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