Discussion
T2D, thrombocytopenia, hypoglycemia, hyperglycemia, hypoglycemia unawareness, albuminuria
HYPOGLYCEMIA UNAWARENESS, ADVERSE EVENTS, THROMBOCYTOPENIA, NOCTURNAL HYPOGLYCEMIA, ADVERSE EFFECT, DISORDERS, HYPOGLYCEMIA, ADVERSE EFFECTS, HYPERGLYCEMIA, SYNDROMES
Here, we present the results of the STREAM study, a new randomized controlled trial that demonstrated the efficacy and safety of sitagliptin treatment in older T2D patients with moderate glycemic control. Improvements in the glycemic parameters were significantly greater in sitagliptin group than control group. In addition, the present study revealed that sitagliptin treatment improved albuminuria in older T2D patients. In the safety analyses, the incidence rate of adverse events did not differ between the two groups; however, sitagliptin treatment increased serum CysC levels and likely induced platelet count reduction. However, these laboratory adverse effects were not considered severe because there were no cases in which adverse effects developed to grade 3 as defined in the CTCAE.In the present study, HbA1c levels decreased by 0.61% in sitagliptin group. The magnitude of HbA1c reduction by sitagliptin treatment was similar to that observed in a study on a combination therapy with sitagliptin and insulinNotably, sitagliptin group showed a significant decrease in eGFR in association with significantly increased levels of Cr and CysC compared with control group. In contrast, a reduction in uACR was observed in sitagliptin group, suggesting that sitagliptin treatment may improve glomerular hyperfiltration. Such changes in renal function parameters after sitagliptin treatment are consistent with previous reports, including our ownIn the present study, adverse events were reported in both groups. Episodes of hypoglycemia were observed in one case in each group, but none of the patients developed severe hypoglycemia or dropped out due to hypoglycemia. In a randomized controlled study comparing treatment with sitagliptin and placebo, sitagliptin monotherapy did not cause hypoglycemia in 206 older T2DIn the laboratory adverse effect analysis, a decreased platelet count was noted in five cases in sitagliptin group, although there was no between-group difference. In fact, six cases of thrombocytopenia have been reported in patients treated with sitagliptin during post-marketing surveillance performed in JapanThe present study had several limitations. First, the number of participants was relatively small. Second, older adults tend to have health problems, such as geriatric syndromes and impairments in physical and cognitive function, but we did not assess these disorders. Further studies stratified by the levels of cognitive function and activity of daily living are necessary to evaluate the risk and benefit of sitagliptin treatment in older adults with T2D. Third, the protocol did not refer to the changes in antihypertensives, lipid-lowering drugs, and other concomitant mediations. Therefore, we could not exclude a possibility that changes in these drugs might influence on renal function and also on glucose metabolism. Lastly, participants did not perform self-measurement of blood glucose (SMBG) or intermittently scanned continuous glucose monitoring (isCGM) during the treatment period. This means that occurrences of hypoglycemia unawareness and nocturnal hypoglycemia could not be ascertained in the present study.In conclusion, the STREAM study revealed that sitagliptin treatment effectively improved the glycemic profile without any serious adverse effects, including self-reported hypoglycemia, in older T2D patients. Therefore, we consider sitagliptin as an ideal candidate to achieve better glycemic control in older adults with T2D who have persistent hyperglycemia under current lifestyle interventions and anti-diabetic drug regimens without GLP-1-based drugs.