32 (58%) of 55 patients had grade 3 or worse treatment-related adverse events, the most frequent being hypertension in 16 (29%) patients and increased concentrations of alanine aminotransferase, amylase, and lipase, and palmar-plantar erythrodysaesthesia syndrome in four (7%) patients each.
There were no deaths related to adverse events and the most frequent grade 3 or higher adverse events were hypertension (11 [31%] of 36 patients), neutropenia (four [11%]), increased concentrations of alanine aminotransferase (four [11%]), and increased concentrations of bilirubin (three [8%]).
Conclusion Higher ALT and AST levels were found in T2DM patients but with no statistically significant link between elevated levels and gender, age, BMI, HbA1c, TG, TC, HDL-C, LDL-C, smoking, or hypertension.
The most common adverse events reported in all patients, regardless of dose group, included fatigue (74.3%), diarrhea (47.1%), increased alanine aminotransferase (37.1%), headache (35.7%), hypertension (35.7%), and nausea (35.7%); overall, 34 (48.6%) patients experienced adverse events that resulted in dose reductions.
The most frequent grade 3 adverse events were hypertension (nine [35%] of 26 patients), increased concentration of alanine aminotransferase (six [23%]), and increased aspartate aminotransferase (five [19%]).
In all treated patients, the most common grade 3-4 treatment-related adverse events in the nivolumab and ipilimumab group were increased lipase (57 [10%] of 547), increased amylase (31 [6%]), and increased alanine aminotransferase (28 [5%]), whereas in the sunitinib group they were hypertension (90 [17%] of 535), fatigue (51 [10%]), and palmar-plantar erythrodysaesthesia (49 [9%]).
The most common grade 3-4 treatment-emergent adverse events were hypertension (43 [11%] patients in the radium-223 group vs 52 [13%] patients in the placebo group), fractures (36 [9%] vs 12 [3%]) and increased alanine aminotransferase concentrations (34 [9%] vs 28 [7%]).
After adjusting for potential confounding variables, the association of hypertension and ALT level was only significant in women: for each 1 IU/L elevation of ALT level, the adjusted odds ratio (OR), and corresponding 95% confidence interval (CI) of hypertension was 1.04 (1.01, 1.07); the ORs of hypertension increased across tertiles of ALT, and the ORs (95% CIs) were 1.00, 1.17 (0.85, 1.60), and 1.63 (1.15, 2.31 (P value for trend = .021).
Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A<sub>1c</sub> , white blood cell count and the presence of hypertension were selected.