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. 2024 Jul 18;4(1):145.
doi: 10.1038/s43856-024-00556-1.

Precision treatment of beta-cell monogenic diabetes: a systematic review

Rochelle N Naylor  1 , Kashyap A Patel #  2 , Jarno L T Kettunen #  3   4   5 , Jonna M E Männistö #  6   7 , Julie Støy #  8 , Jacques Beltrand  9 , Michel Polak  10   11   12 ; ADA/EASD PMDI; Tina Vilsbøll  13 , Siri A W Greeley  1 , Andrew T Hattersley  2 , Tiinamaija Tuomi  14   15   16   17
Collaborators, Affiliations

Precision treatment of beta-cell monogenic diabetes: a systematic review

Rochelle N Naylor et al. Commun Med (Lond). .

Abstract

Background: Beta-cell monogenic forms of diabetes have strong support for precision medicine. We systematically analyzed evidence for precision treatments for GCK-related hyperglycemia, HNF1A-, HNF4A- and HNF1B-diabetes, and mitochondrial diabetes (MD) due to m.3243 A > G variant, 6q24-transient neonatal diabetes mellitus (TND) and SLC19A2-diabetes.

Methods: The search of PubMed, MEDLINE, and Embase for individual and group level data for glycemic outcomes using inclusion (English, original articles written after 1992) and exclusion (VUS, multiple diabetes types, absent/aggregated treatment effect measures) criteria. The risk of bias was assessed using NHLBI study-quality assessment tools. Data extracted from Covidence were summarized and presented as descriptive statistics in tables and text.

Results: There are 146 studies included, with only six being experimental studies. For GCK-related hyperglycemia, the six studies (35 individuals) assessing therapy discontinuation show no HbA1c deterioration. A randomized trial (18 individuals per group) shows that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes. Cohort and case studies support SU's effectiveness in lowering HbA1c. Two cross-over trials (each with 15-16 individuals) suggest glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes is limited. Most reported patients with HNF1B-diabetes (N = 293) and MD (N = 233) are on insulin without treatment studies. Limited data support oral agents after relapse in 6q24-TND and for thiamine improving glycemic control and reducing/eliminating insulin requirement in SLC19A2-diabetes.

Conclusion: There is limited evidence, and with moderate or serious risk of bias, to guide monogenic diabetes treatment. Further evidence is needed to examine the optimum treatment in monogenic subtypes.

Plain language summary

Monogenic diabetes is a type of diabetes caused by changes in genes that affect how the body makes or responds to insulin. Precision medicine (where knowledge of the gene change directs the selection of treatment) is available for some forms of monogenic diabetes. This study evaluated the published literature for several forms of monogenic diabetes to assess the level of evidence supporting specific precision treatments. Among the 146 small studies that we reviewed, only six compared different treatments. However, we found evidence supporting oral medications for some types of monogenic diabetes, and evidence that treatment is not needed for one particular type. Based on our results, we provide treatment recommendations for certain forms of monogenic diabetes and identify future directions for research to help us optimize precision medicine in monogenic diabetes.

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Conflict of interest statement

J.K. has received lecture fees from NovoNordisk, international conference costs covered by Medtronic, AstraZeneca, and NovoNordisk; M.P. has been the scientific advisor for the AMGLIDIA (glibenclamide suspension) development; TV has served on scientific advisory panels, been part of speaker’s bureaus, and served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. All other authors declare no competing interests.

Update of

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