Aims: To report final results of an open label phase II trial, which evaluated outcomes of PMF patients after 24mo on MTF treatment. Phase III studies are required to confirm our results and to evaluate whether MTF treatment in early PMF phases could delay the progression of BM fibrosis through the downregulation of the JAK-STAT pathway.

In JAK2-mutated cell lines, MTF reduced cell viability, proliferation and clonogenicity, while in Jak2V617F knock-in-induced mice, MTF reduced Ba/F3 JAK2V617F tumor burden and splenomegaly. PCR array for insulin signaling genes showed 21 genes downregulated after 6 months of MTF treatment, including genes previously associated with MPN phenotype: INS, NOS2, VEGFA, LEP, IGFBP1 and IRS2.

A clinical trial evaluating the efficacy and safety of metformin and simvastatin (M+S) in patients with muscle invasive urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy has identified no unexpected or unacceptable toxicity. However, the treatment was found to have no significant effect on Ki67, a marker of proliferation, or pmTOR IHC labelling. Nevertheless, promising efficacy was seen in reducing PI3K/Akt/mTOR signalling, with only one patient experiencing grade 2 diarrhea, and several receiving dose modification. Interim analysis at one year identified a sample size of just 12 patients to be studied, with two patients having received neoadjuvant chemotherapy. Nonetheless, the study is seen as promising, with trial enrolment continuing. The research was funded by the Physician Services Incorporated, Bladder Cancer Canada, Canadian Urologic Oncology Group, London Regional Cancer Program and the Department of Surgery, University of Western Ontario.

A systematic review and meta-analysis has found no significant association between metformin use and a lower risk of biliary tract cancer (BTC) or improved prognosis in people with BTC. The analysis focused on 11 studies with a total of 24,788,738 participants, comparing risk, overall survival (OS), and disease-free survival (DFS) in patients with BTC. The results showed no significant differences in BTC risk, OS, or DFS between metformin users and non-users, and the same negative result was found when restricted to participants with diabetes. However, the included studies exhibited significant heterogeneity in the selection of participants and the definition of metformin users, leading the authors to caution against overinterpretation of the results. Further studies are warranted to determine the optimal timing, dose, duration, and scenario of metformin administration in relation to BTC risk and prognosis.

A study conducted in Korea evaluated the effects of Teneligliptin, a diabetes drug, on glycosylated hemoglobin (HbA1c) levels in elderly type 2 diabetes mellitus patients. The randomized, double-blind, placebo-controlled study recruited 65 participants aged 65 years or higher who were treatment-naïve or had been treated with stable doses of metformin. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability. After 12 weeks, a significant reduction in HbA1c levels was observed in the Teneligliptin group compared to that in the placebo group. Furthermore, the treatment significantly decreased the time spent above the target range and glycemic variability without increasing hypoglycemia in the study population. The study concluded that Teneligliptin effectively reduced HbA1c levels and glycemic variability in elderly type 2 diabetes mellitus patients without increasing the risk of hypoglycemia.

A combination of metformin and spironolactone could be more effective for the treatment of polycystic ovarian syndrome (PCOS) than either drug alone, according to a study from Guangzhou Medical University. The research was a single-centre, randomised, open-label, pilot study involving 189 patients with PCOS. Participants were given metformin, spironolactone or a mix of the two in a ratio of 1:1:1. The study measured the change in homeostatic model assessment (HOMA)-IR after 12 weeks. It revealed that the combined therapy was more effective in lowering HOMA-IR than the two respective monotherapies. Both metformin and spironolactone reduced HOMA-IR in those with PCOS, though without significant differences between the two single-drug treatments. The trial also observed lower levels of total testosterone and free androgen index in the combination therapy than in the metformin group. Similarly, total testosterone levels, FAI, HOMA-β, fasting plasma glucose, and AUCins were lower in the spironolactone group than in the metformin group.

A new study has found that metformin delayed-release (Metformin DR) may be an effective treatment for type 2 diabetes in patients with renal impairment. The study evaluated the glycemic effects and safety of Metformin DR, which targets the delivery of metformin to the ileum to minimise systemic exposure, compared to a placebo and immediately released metformin in patients with type 2 diabetes. The study found that Metformin DR exhibited greater efficacy per unit of plasma exposure than Metformin IR, and reduced HbA1c and fasting plasma glucose (FPG) levels. However, normalising efficacy to systemic exposure, glycemic improvements with Metformin DR were still 1.5-fold greater than with metformin IR for HbA1c and 2.1-fold greater for FPG. Adverse events were primarily gastrointestinal but were less frequent with Metformin DR (<16% incidence) than with Metformin IR (28%), especially nausea. The results of the study suggest that Metformin DR may provide an effective treatment option for type 2 diabetes patients with advanced renal disease, where metformin use is generally restricted.

A trial has found that patients starting glucocorticoids are less likely to experience metabolic complications when taking metformin. In a double-blind, placebo-controlled trial, patients took glucocorticoid treatment and were given either metformin or a placebo. The primary endpoint was the change in the 2-hour area under the curve of glucose during the oral glucose tolerance test between baseline and four weeks. After the trial, 29 of the 34 non-diabetic patients had completed it. It was found that those taking a placebo had increased levels of glucose, whereas those in the metformin group did not. This change within four weeks was different between both groups. The study concluded that metformin “seems to be a promising drug for preventing metabolic side effects during systemic glucocorticoid treatment”.

Researchers involved in the SPIOMET4HEALTH project, funded by the European Commission, are set to begin a trial aimed at reducing ectopic fat in adolescent girls and young women with Polycystic Ovary Syndrome (PCOS). The event will be Europe-wide and take place in seven certified centers. There is presently no FDA-approved treatment for adolescent PCOS, which is characterized by androgen excess and oligo-anovulation. A combination of standardized lifestyle intervention and pharmacological addendum is expected to help alleviate symptoms of the condition, with low-dose pioglitazone, spironolactone and metformin, all known for their insulin-sensitizing and gonadotropin-normalizing properties, added to placebo or SPIOMET (brand name of active ingredient). A total of 364 patients with "adolescent PCOS" (12–23.9 years old, BMI <35 kg/m2) are expected to be enrolled, with follow-up post-treatment lasting six months. The trial aims to assess whether the fixed dose combination of SPIOMET is a safe, effective and tolerable treatment for this syndrome.

A study has suggested that combining nivolumab, a programmed cell death protein 1 (PD-1) blocking immune checkpoint inhibitor, with the hypoglycaemic agent metformin may have antitumour effects. The study aimed to investigate the safety and efficacy of the nivolumab-metformin combination in diabetic patients with melanoma, renal cell carcinoma or lung cancer. The concomitant use of nivolumab and metformin was found to be well tolerated, with adverse events limited to fatigue, pruritus, rash, and asthenia experienced by 75% of patients, whilst grade 3 adverse events occurred in only 20% of cases. A significant correlation was established between higher daily doses of metformin (>1,000 mg daily) and longer progression-free survival, overall survival, and higher overall response rates. The conclusion of the study was that combining the two drugs was safe and potentially antitumour, supporting further investigation into their synergistic impact.