Research in brief

Abstract

In a phase 2, dose-ranging study, researchers assessed patiromer twice a day for treating hyperkalaemia in people with type 2 diabetes and chronic kidney disease who were already receiving renin-angiotensin-aldosterone system inhibitors (n=306). After about 4 weeks, investigators noted a reduction in serum potassium concentration compared with baseline in participants with mild hyperkalaemia (starting dose 8·4 g: least squares mean reduction 0·35 mmol/L [95% CI 0·22–0·48]; 16·8 g group: 0·51 mmol/L [0·38–0·64]; 25·2 g group: 0·55 mmol/L [0·42–0·68]). Across the various dose groups, serum potassium also decreased in participants with moderate hyperkalaemia (p<0·001 for comparisons with baseline across the different groups and doses). Risk of cancer with pioglitazone use was assessed in a diabetes registry study by Lewis and colleagues. Researchers included a cohort of 193 099 individuals for the bladder cancer analysis, 18% (34 181) of whom had used pioglitazone for a median of 2·8 years (range 0·2–13·2). Bladder cancer occurred in 1261 individuals, with adjusted analysis indicative of no significant association between pioglitazone and bladder cancer (adjusted hazard ratio [aHR] for ever-use of pioglitazone 1·06, 95% CI 0·89–1·26); these results were supported in a case-control analysis. In the cohort of 236 507 individuals included in the analysis of ten other cancers, an association between pioglitazone ever-use and prostate cancer (aHR 1·13, 95% CI 1·02–1·26) and pancreatic cancer (1·41, 1·16–1·71) was noted; the researchers concluded that these results, “…merit further investigation to assess whether the observed associations are causal or due to chance, residual confounding, or reverse causality”. Results from a phase 2, dose-ranging study pave the way for a phase 3 trial of ISIS 304801. In the double-blind trial, researchers randomly allocated patients with hypertriglyceridaemia to receive either weekly ISIS 304801 or placebo for 13 weeks. Participants who received placebo monotherapy (n=16) showed an increase in plasma APOC3 concentration from baseline (mean change 4·2% [SD 41·7]), whereas participants who received active treatment (n=35) showed reductions in APOC3 concentration (100 mg: −40·0% [32·0]; p<0·05 compared with placebo; 200 mg: −63·8% [22·3]; p<0·001; 300 mg: −79·6% [9·3]; p<0·001). Participants who received active treatment in addition to continued fibrate therapy (n=18) also had greater reductions in APOC3 concentrations than the eight participants who received placebo plus fibrate (p<0·001). APOC3 lowering was associated with reductions in triglycerides. As part of a prospective observational study, Olsen and colleagues have described the baseline characteristics of a cohort of young people with gender dysphoria. Participants were aged 12–24 years and were seen in a transgender youth clinic in Los Angeles, CA, USA. 51 (50%) of 101 participants were of female gender at birth (transmasculine). Baseline mean testosterone in the transmasculine cohort was 1·48 nmol/L (SD 1·43; normal female range 0·07–1·56); one (2%) participant had a virilising disorder, and four (8%) had polycystic ovarian syndrome. In transfeminine youth, baseline mean estradiol was 101 pmol/L (SD 46; normal male range <106), and prolactin was 0·35 nmol/L (0·17; normal range 0·09–0·78). Extension of the 2-year DATA trial provides insight into the effect of switching between teriparatide and denosumab treatment in women with postmenopausal osteoporosis. Women who were originally assigned to teriparatide (20 mg per day) were switched to denosumab (n=27), those who had received denosumab (60 mg every 6 months) were switched to teriparatide (n=27), and women who had received combination therapy were transitioned to denosumab (n=23). At the end of the 2-year extension, mean spine bone mineral density (BMD) continued to increase in all treatment groups, although switching from denosumab to teriparatide led to a transient decrease before BMD increased. Switching to teriparatide led to initial decreased hip BMD, whereas BMD continued to increase in the other groups, with greatest increases in the group originally receiving combination therapy (p<0·05). In an ongoing extension study of postmenopausal osteoporosis, the effect of long-term denosumab treatment was assessed. After completion of the 3-year placebo versus denosumab FREEDOM study, all women received denosumab for an additional 5 years (denosumab continuation, n=2343; placebo crossover, n=2207). In participants originally allocated to denosumab, BMD continued to increase relative to extension baseline at the hip (8·3%), femoral neck (7·8%), lumbar spine (18·4%), and radius (3·5%; p<0·05 for all). Women who switched from placebo to denosumab had increases in BMD at hip (6·2%), femoral neck (5·7%), lumbar spine (18·4%), and radius (1·5%; p<0·05 for all). During the extension phase, eight cases of osteonecrosis of the jaw and two atypical femoral fractures were reported.