Dear Editor,
We have read with interest the article on treatment of latent autoimmune diabetes in adults (LADA) by Lin Yang and coworkers, titled “Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial” (1). We agree with the authors that the scarcity of studies on treatment in this common form of diabetes strongly motivates the conducting of randomized clinical trials such as the present one. Additionally, we would like to commend the frequent use of well-validated meal tests as the stated primary outcome parameter for assessing beta cell function during the 24 months of the study.
We doubt, however, whether the conclusions of the authors are valid—namely, that addition of sitagliptin, a dipeptidyl peptidase 4 inhibitor, to an insulin regimen has indeed beneficial effects on the preservation of beta cell capacity in the LADA participants.
Our concerns are the following:
1) As to results of meal tests, the authors report mainly data within the 2 arms of the study, namely, insulin plus sitagliptin, labeled SITA, and only insulin, labeled CONT (Table 2 of the paper). The only significant effect for SITA vs CONT (lower C-peptide in CONT) was recorded after 12 months. However, at 24 months (end of study), the C-peptide responses appear identical in SITA and CONT, hence no preferential effects.
2) A larger number of participants in SITA than in CONT were excluded during the study because of bad metabolic control, raising the possibility of bias (since deterioration of C-peptide is a major cause of bad metabolic control). Did the authors perform an intention-to-treat analysis? If so, what was the result of such analysis?
3) The authors emphasize homeostatic model assessment (HOMA)-beta results. This seems questionable, since HOMA-beta is in general not amenable to evaluation in insulin-treated subjects (2).
4) Hyperglycemic and euglycemic clamps were performed but only in 6 participants each in SITA and CONT and it is unclear to which extent these few participants are representative for the study population, n = 25 × 2, in toto.
We reiterate that the present study fulfills a need for randomized controlled trials in LADA patients. However, the evidence provided does not in our view in any way motivate the addition of a dipeptidyl peptidase 4 inhibitor to insulin treatment in such patients. In this context, it may be relevant to mention that our own randomized controlled trial (3) comparing insulin with sitagliptin treatment did not reveal any obvious beneficial effect on insulin secretion of the latter.
Glossary
Abbreviations
- HOMA-beta
homeostatic model assessment for beta cell function
- LADA
latent autoimmune diabetes in adults
Additional Information
Disclosures: The authors have reported that they have no conflicts of interest to disclose. All authors have submitted the International Committee of Medical Journal Editors Form for Disclosure of Potential Conflicts of Interest.
References
- 1.Yang L, Liang H, Liu X, et al. Islet function and insulin sensitivity in latent autoimmune diabetes in adults taking sitagliptin: a randomized trial. J Clin Endocrinol Metab. 2021;106(4):e1529-e1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27(6):1487-1495. [DOI] [PubMed] [Google Scholar]
- 3.Hals IK, Fiskvik Fleiner H, Reimers N, et al. Investigating optimal β-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019;21(10):2219-2227. [DOI] [PubMed] [Google Scholar]
