Evidence map›Paper›PMID 40665260›Full record

SynthesisBMC endocrine disorders2025

The effects of non-insulin anti-diabetic medications on the diabetic microvascular complications: a systematic review and meta-analysis of randomized clinical trials.

Song Wen, Yue Yuan, Yanyan Li, Chenglin Xu, Lijiao Chen, Yishu Ren, Congcong Wang, Yanju He, Xiucai Li, Min Gong and 4 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC endocrine disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Observational
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Song Wen *Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. 379295093@qq.com.
Yue Yuan *Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Yanyan LiDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Chenglin XuDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Lijiao ChenDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Yishu RenDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Congcong WangDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Yanju HeDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Xiucai LiDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Min GongDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Xinlu YuanDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Dongxiang XuDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Chaoxun WangDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China.
Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. zhouligang1n1@163.com.

Funding

Fudan Good Practice Program of Teaching and Learning FD2023A227Fudan Zhangjiang Clinical Medicine Innovation Fund Project KP0202118Integrated Traditional Chinese and Western Medicine YC-2023-0404
6 · The paper itself

Abstract

introductionAlthough the onset and progression of diabetic microvascular complications are linked to glycemic control, various antihyperglycemic drugs with distinct treatment targets may positively impact microvascular lesions beyond their glucose-lowering effects. Therefore, this systematic review emphasizes the clinical therapeutic implications of non-insulin anti-diabetic medications for diabetic microvascular complications.

methodsWe retrieved published literature reporting randomized clinical trials (RCTs) on the effects of microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR), from authenticated clinical databases: PubMed, Excerpta Medica database (EMBASE), and Web of Science. We synthesized data, including the continuous variable indices: estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), and urinary albumin excretion rate (UAE). Indices measuring cardiovascular autonomic neuropathy (CAN), vibration detection threshold (VDT), and retinal nerve fiber thickness (RNFL) were used to calculate microvascular effects. We also synthesized dichotomous variable indices, including the risks for DR and DPN.

resultsAccording to our analyses, there was sparse evidence strongly supporting that metformin (MET), Sulfonylurea (SUs), Repaglinide (Repa), or α-Glucosidase inhibitors (α-GIs) could benefit diabetic microvascular complications when adopted as monotherapy. Regardless of the no change in eGFR, two trials reporting Thiazolidinediones (TZDs) significantly reduced the UACR, while other clinical trials reported an increase in VDT and improvement in DR. Sodium glucose co-transporter inhibitors (SGLT-2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA) both showed protective effects in preventing eGFR decline, with only SGLT-2i demonstrating a significant reduction in UACR. A recent trial showed that Dipeptidyl Peptidase IV inhibitors (DPP-IVi) may potentially reduce the risk of DPN, while GLP-1RA did not prove to alter the measures of CAN and DPN. However, the SUSTAIN 6 trial revealed that Semaglutide may increase the risk of DR.

conclusionBesides their anti-hyperglycemic properties, some currently reviewed medications may exhibit unique anti-microvascular abilities. Due to ambiguous and conflicting available results, more emerging or ongoing trials will address this issue and could benefit clinical strategies for personalized treatment practices. CLINICAL TRIAL NUMBER: Not applicable.

Indexed as

Diabetes Mellitus, Type 2Diabetic AngiopathiesDiabetic NephropathiesDiabetic NeuropathiesDiabetic RetinopathyHypoglycemic AgentsHumansRandomized Controlled Trials as TopicHypoglycemic AgentsDiabetic microvascular complicationDiabetic nephropathyDiabetic neuropathyDiabetic retinopathyNon-insulin anti-diabetic medication

Identifiers

PMID40665260
PMCPMC12265122

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.