While CSII therapy is commonly used in the management of type 1 diabetes, less is known about its use in patients with T2D. Further, there is a paucity of information on the combined use of CSII with oral glucose-lowering medications even though insulin therapy along with oral hypoglycemics are often used in T2D to overcome insulin resistance and improve glycemic control.

Researchers conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) from eight databases, including PubMed, Embase, Cochrane Library, Web of Science, and four Chinese databases (CNKL, VP-CSFD, WANFANG, and CBM) from their inception through June 27, 2021, to evaluate the clinical efficacy of combination therapy of CSII with six classes of oral hypoglycemics (thiazolidinediones [TZDs], metformin, acarbose, glucagon-like peptide [GLP]-1 receptor agonists [RA], sodium-glucose cotransporter [SGLT]-2 inhibitors, and dipeptidyl peptidase [DPP]-4 inhibitors) in patients with T2D.

To be included in this study, eligible RCTs needed to report on patients with T2D; had to compare CSII alone and CSII combined with one of the six oral hypoglycemic agents; and had to report on the following outcomes: blood glucose indexes before and after treatment (fasting plasma glucose [FPG], 2-hour postmeal blood glucose [2h PG], hemoglobin A1c [HbA1c]), islet function (fasting C-peptide, 2-hour post-meal C-peptide, beta-cell function [HOMA-beta]), insulin resistance index (HOMA-IR), blood glucose standard time, and insulin dosage. HOMA, or homeostatic model assessment, is a method of assessing beta-cell function and insulin resistance using fasting glucose and insulin or C-peptide concentrations.

RCTs were excluded from analysis if they included patients with T2D and other diseases (this was not clarified); the study research design was not clearly defined; data on desired outcomes were not available; if papers were duplicates; if the full text of the article was not available; and if study patients had cardiovascular disease, hypertension, cancer, chronic kidney disease, and other (undefined) T2D. Sulfonylureas were not included in this analysis since there were too few RCTs that utilized this class of hypoglycemics and the risk of hypoglycemia would be greatly enhanced if combined with CSII.

Investigators found 56 publications that involved 4,184 patients with T2D on CSII that met the inclusion criteria. The risk of bias was high in 52 out of the 56 studies. Not every RCT included identified all of the desired outcomes.

A ranking of efficacy of CSII combination therapy on FPG found that metformin had the largest reduction in FPG, followed by DPP-4 inhibitors, acarbose, TZDs, and GLP-4 RAs; no data on FPG were available for SGLT-2 inhibitors. A ranking of efficacy of CSII combination therapy on 2h PG showed that metformin was associated with the largest reduction in 2h PG followed by DPP-4 inhibitors, GLP-1 RA, TZDs, and acarbose; no information was available on 2h PG for SGLT-2 inhibitors. A ranking of efficacy of CSII combination on HbA1c found that DPP-4 inhibitors had the largest reduction in HbA1c, followed by GLP-1 RAs, TZDs, metformin, and acarbose; no data were available on the effects of SGLT-2 inhibitors on HbA1c.

When the effects of combination CSII therapy was determined on insulin resistance and HOMA-IR, metformin showed the largest reduction in HOMA-IR, followed by DPP-4 inhibitors, TZDs, GLP-1 RAs, and SLGT-2 inhibitors; no information was available for acarbose's effects on HOMA-IR. When determining the amount of insulin required with combination CSII therapy, GLP-1 RAs required the least amount of insulin, followed by SGLT-2 inhibitors, acarbose, metformin, DPP-4 inhibitors, and TZDs. Last, DPP4-inhbitors when used in combination with CSII were most often associated with the shortest amount of time to reach blood glucose standards. In rank order, DPP4-inhibitors were followed by SLGT-2 inhibitors, acarbose, metformin, and TZDs for the time to reach blood glucose standards; no data were available for GLP-1 RA on how long they took to reach standard blood glucose levels.

Limitations of this article were that it included studies that had poor methodological quality and a high risk for bias, there was heterogeneity among the study populations, and there were missing data.

As the population continues to grow older and there is an increase in the prevalence of T2D, this systematic review and meta-analysis provides useful information for pharmacists managing patients who are on combination therapy with insulin and an oral hypoglycemic agent.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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