This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy.

Lung cancer remains a challenge in daily practice. Chemotherapy is first considered for advanced lung adenocarcinoma bearing no active driver mutations. Maintaining drug efficacy and overcoming drug resistance are essential. This study aimed to explore the real-world use of anti-diabetic agent metformin in combination with pemetrexed-based platinum doublets in a first-line setting. We retrospectively collected data during 2004~2013 from TaiwaN′s National Health Insurance Research Database to access the survival benefit of metformin combined with pemetrexed-based platinum doublets as a first-line therapy for diabetic patients with advanced lung adenocarcinoma. Demographic data and information regarding platinum reagents, diabetes medications, and metformin doses were gathered, and overall survival status regarding metformin use was analyzed. Overall survival status based on the daily dose and the calculated cumulative defined daily dose (DDD) of metformin prescribed during the first 3 months after lung cancer was diagnosed was also assessed. A total of 495 patients were enrolled with a mean age of 67 years old, and the majority of the patients were male. After adjusting for age, sex, diabetes medication, and platinum reagents used, the adjusted hazard ratio (HR) for the metformin-user group was 0.61 (95% confidence interval (CI); 0.46~0.79; p < 0.001). The metformin-user group had a survival benefit (log-rank p < 0.001). We analyzed metformin dosing during the first 3 months after lung cancer diagnosis, and for a daily dose ≥ 1500 mg, the adjusted hazard ratio (aHR) was 0.42 (95% CI; 0.27~0.65; p < 0.001). Regarding the cumulative DDD of metformin, a DDD equal to or exceeding 21 resulted in aHR of 0.48 (95% CI; 0.34~0.69; p < 0.001). In this study, we found that the combination of metformin and pemetrexed-based platinum doublets provides a robust survival benefit as a first-line therapy for diabetic patients with advanced lung adenocarcinoma. It is worth conducting a large and randomized clinical trial to further investigate the antitumor effects of metformin on advanced lung adenocarcinoma when used as a first-ling therapy, including in non-diabetic patients.

Objective: An increasing trend in the prevalence of gestational diabetes mellitus (GDM) has been reported in Taiwan. GDM has been linked to various adverse maternal outcomes over a long period, including cardiovascular disease (CVD) and chronic kidney disease (CKD). However, evidence implies that the effects of GDM on the mid-term surrogate risk factors for these diseases are limited. Furthermore, data from nationwide cohort studies are limited. The primary aim of this study was to investigate the risk of developing type 2 diabetes mellitus (T2DM), arterial hypertension (aHTN), and hyperlipidemia (HL) through a 5-year follow-up post-delivery of women with GDM in a nationwide cohort study in Taiwan. The second objective was to investigate the risk of developing insulin resistance syndrome (IRS)-related diseases, including CVD, acute myocardial infarction (AMI), peripheral artery occlusive disease (PAOD), non-alcoholic fatty liver diseases (NAFLD), and CKD. Methods: This was a retrospective, population-based nationwide cohort study. The data source comprises a merge of the Birth Certificate Application Database (BCA) and the National Health Insurance Research Database in Taiwan. Women aged between 15 and 45 years who gave birth in Taiwan between 2004 and 2011 were included. Women who were enrolled and had a GDM diagnosis were assigned to the exposure group. Women who were enrolled without a GDM diagnosis were assigned to the comparison group. The relative risk of developing T2DM, aHTN, HL, and IRS-related diseases, including CVD, AMI, PAOD, NAFLD, and CKD, were analyzed and presented as hazard ratio (HR) through Cox regression and log-rank regression analyses. Results: A total of 1,180,477 women were identified through the BCA database between 2004 and 2011. Of those, 71,611 GDM-diagnosed women and 286,444 women without GDM were included in the final analysis. After adjusting for age, pre-existing cancer, and parity, developing T2DM, aHTN, and HL were still significantly increased in the GDM group (HR and interquartile range (IQR): 2.83 (2.59, 3.08), 1.09 (1.01, 1.06), and 1.29 (1.20, 1.38), accordingly). CVD, NAFLD, and CKD had a very low incidence and showed insignificant results. Conclusion: Our findings provide nationwide cohort data showing that GDM increased the risk of developing T2DM, aHTN, and HL 5 years after delivery within the same group. The GDM complications and risk of CVD, AMI, PAOD, NAFLD, and CKD need further investigation.