OBJECTIVE: Tirzepatide is a first-in-class combination glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP1-RA) approved for treatment of adults with type 2 diabetes mellitus (T2DM) and chronic weight management. The aim of this analysis was to assess the real-world efficacy of tirzepatide in patients with T2DM.
METHODS: This retrospective observational study evaluated patients with T2DM from a large urban academic medical centre who received at least 3 months of continuous tirzepatide treatment. The primary outcome was change in A1C from following tirzepatide treatment. Secondary outcomes included change in body weight and body mass index (BMI) after tirzepatide was initiated.
RESULTS: A total of 1896 patient charts were reviewed, and 612 patients were evaluated for the primary outcome. Over a median time period of 10.4 months, treatment with tirzepatide resulted in a mean A1C reduction of 1.02 ± 1.48% (p < 0.001). A total of 570 patients were evaluated for the secondary outcomes. Tirzepatide was associated with a mean reduction in body weight of 7.3 ± 9.3 kg (p < 0.001) and a mean reduction in BMI of 2.5 kg/m2. Greater A1C lowering and weight loss was observed in patients without prior GLP1-RA treatment compared to those switched to tirzepatide from GLP1-RA.
CONCLUSIONS: In a real-world population of US patients with T2DM, tirzepatide was associated with clinically and statistically significant reductions in A1C and body weight. Greater reductions in both A1C and body weight were observed among patients who were GLP1-RA naïve compared to patients switched from GLP1-RA to tirzepatide.

BACKGROUND: Lifestyle interventions are key to the control of diabetes and the prevention of complications, especially when used with pharmacological interventions. This protocol aims to review the effectiveness of lifestyle interventions in relation to nutrition and physical activity within the West African region. This systematic review and meta-analysis seeks to understand which interventions for lifestyle modification are implemented for the control of diabetes in West Africa at the individual and community level, what evidence is available on their effectiveness in improving glycaemic control and why these interventions were effective.
METHODS: We will review randomised control trials and quasi-experimental designs on interventions relating to physical activity and nutrition in West Africa. Language will be restricted to English and French as these are the most widely spoken languages in the region. No other filters will be applied. Searching will involve four electronic databases - PubMed, Scopus, Africa Journals Online and Cairn.info using natural-language phrases plus reference/citation checking. Two reviewers will independently screen results according to titles and abstracts against the inclusion and exclusion criteria to identify eligible studies. Upon full-text review, all selected studies will be assessed using Cochrane\'s Collaboration tool for assessing the risk of bias of a study and the ROBINS-I tool before data extraction. Evidence will be synthesised narratively and statistically where appropriate. We will conduct a meta-analysis when the interventions and contexts are similar enough for pooling and compare the treatment effects of the interventions in rural to urban settings and short term to long term wherever possible.
CONCLUSIONS: We anticipate finding a number of studies missed by previous reviews and providing evidence of the effectiveness of different nutrition and physical activity interventions within the context of West Africa. This knowledge will support practitioners and policymakers in the design of interventions that are fit for context and purpose within the West African region.
BACKGROUND: This systematic review has been registered in the International Prospective Register for Systematic Reviews - PROSPERO, with registration number CRD42023435116. All amendments to this protocol during the process of the review will be explained accordingly.

OBJECTIVE: To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D).
METHODS: We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication.
RESULTS: A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications.
CONCLUSIONS: In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures.

OBJECTIVE: To assess and compare the therapeutic efficacy of Liraglutide, Tirzepatide, and Retatrutide in treating diabetic kidney disease (DKD) in db/db mice.
METHODS: Db/db mice were administered intraperitoneal injections of Liraglutide (10 nmol/kg), Tirzepatide (10 nmol/kg), and Retatrutide (10 nmol/kg) for 10 weeks. Subsequently, we assessed the effectiveness of these three drugs in controlling blood glucose levels, reducing weight, and improving serum biochemical indicators and DKD. Additionally, we measured and compared the renal inflammation and fibrosis indexes. Meanwhile, the content of intestinal metabolite butyrate was compared to reflect the regulatory effects of these three drugs on gut microbiota.
RESULTS: Retatrutide demonstrated superior effectiveness in reducing weight and improving renal function in db/db mice compared to Liraglutide and Tirzepatide. Additionally, it markedly suppressed the expression of pro-inflammatory cytokines (TNF-α, caspase-1, and NLRP3) and pro-fibrotic factors (fibronectin, α-SMA, and collagen I) in the kidneys of mice. Furthermore, Retatrutide substantially enhanced liver function, reduced triglyceride levels, cholesterol levels, low-density lipoprotein cholesterol, elevated high-density lipoprotein cholesterol, and increased the content of intestinal metabolite butyrate in db/db mice when compared to the other two drugs. Unfortunately, despite its ability to lower blood glucose levels, Retatrutide did not outperform the other two drugs. In contrast, Tirzepatide exhibited better effects on lowering blood glucose, weight loss, lipid reduction, and improvement of DKD compared to Liraglutide.
CONCLUSIONS: Retatrutide and Tirzepatide were significantly effective in improving DKD, controlling blood glucose and body weight. Retatrutide was the most effective in improving DKD and body weight, while Tirzepatide was the most effective in controlling blood glucose. Inhibiting the expression of inflammatory factors and fibrosis mediators and regulating intestinal microbiota may be the potential mechanisms of these two drugs to delay the progression of DKD.

We aimed to evaluate glycaemic control in patients with type 1 diabetes during the first three months of use of the flash glucose monitoring (FGM) system.
METHODS: We conducted a study of a cohort of 81 people with type 1 diabetes mellitus who used the FreeStyle Libre 2 (FSL2) sensor continuously for 3 months. Patients had not used a CGM before. The effectiveness of using the FSL2 system was assessed using AGP reports at two time points (3-4 weeks and 11-12 weeks of system use).
RESULTS: Eight weeks after using FSL2, compared with results from 3-4 weeks of use, there were no differences in the glucose management indicator, time spent in range, above range and below range, or glucose variability. In the first month of FGM use, patients scanned the sensor significantly more often than in the following two months (p = 0.021). No significant differences were found in the change of the evaluated parameters when comparing patients by duration of diabetes and treatment method.
CONCLUSIONS: Short-term use of FSL2 promotes a significant reduction in GMI in patients with more time spent in hyperglycaemia (especially > 250 mg/dL). In this short period of use, no other changes in glycaemic control parameters are observed.

OBJECTIVE: To test the effect of the glucagon-like peptide-1 receptor agonist, liraglutide, on residual beta-cell function in adults with newly diagnosed type 1 diabetes.
METHODS: In a multicentre, double-blind, parallel-group trial, adults with newly diagnosed type 1 diabetes and stimulated C-peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8-mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow-up with only insulin treatment. The primary endpoint was the between-group difference in C-peptide area under the curve (AUC) following a liquid mixed-meal test after 52 weeks of treatment.
RESULTS: Sixty-eight individuals were randomized. After 52 weeks, the 4-hour AUC C-peptide response was maintained with liraglutide, but decreased with placebo (P = .002). Six weeks after end-of-treatment, C-peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo-treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient.
CONCLUSIONS: Treatment with liraglutide improves residual beta-cell function and reduces the dose of insulin during the first year after diagnosis. Beta-cell function was similar at 6 weeks postliraglutide treatment.

BACKGROUND: Anaemia is a global public health issue that impacts individuals of all ages in both developed and developing countries. Anaemia is common in patients with diabetes mellitus; however, it is often undiagnosed and untreated. The main aim of this study was to assess the prevalence and associated factors of anaemia in patients with type 2 diabetes mellitus admitting to a medical unit at National Hospital Kandy.
METHODS: A descriptive, cross-sectional study was conducted in type 2 diabetes mellitus (T2DM) patients admitted to a medical ward at National Hospital Kandy (NHK). They were assessed with a pre-tested, interviewer-administered, structured questionnaire using consecutive sampling method. The data was entered and analyzed using SPSS 26.
RESULTS: Total 252 patients with diabetes were included. The prevalence of anaemia in patients with T2DM was 31.3%. The corresponding values for males and females were 34.2% and 65.8% respectively. Independent predictors for anaemia among diabetic patients were older age, female gender, poor glycemic control, diabetes duration > 5 years, diabetic nephropathy, retinopathy, neuropathy, stage ≥ 3 chronic kidney disease (CKD), ischaemic heart disease (IHD), peripheral vascular disease (PVD), diabetic foot ulcers (DFU) and usage of aspirin. These were significantly associated with the prevalence anemia among patients with type 2 diabetes mellitus. Multivariate logistic regression analysis revealed that female gender, age ≥ 65 years, diabetic duration > 5 years, poor glycaemic control, stage ≥ 3 CKD, diabetic nephropathy and retinopathy were associated with greater odds for the presence of anaemia.
CONCLUSIONS: We found that 31.3% T2DM patients in a medical ward at NHK had previously undiagnosed anaemia. Anaemia screening during diabetes diagnosis, maintaining glycaemic control and raising patient awareness can reduce anaemia prevalence, improve patient quality of life and potentially reduce microvascular complications.

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec and insulin aspart for the treatment of people with diabetes and suboptimal glycaemic control. Few real-world studies of IDegAsp treatment have been conducted. Here, we report results from the Australian cohort of the global ARISE study of real-world IDegAsp use.
OBJECTIVE: To investigate glycaemic control and other clinical outcomes in people with type 2 diabetes (T2D) treated with IDegAsp in a real-world setting in Australia.
METHODS: A total of 183 adults with T2D initiating or switching to IDegAsp in the Australian cohort of the open-label, non-interventional ARISE study were followed for 26-36 weeks from August 2019 to December 2020.
RESULTS: IDegAsp was associated with significant reductions from baseline to end of study (EOS) in mean glycated haemoglobin (estimated change -0.8% (95% confidence interval (CI): -1.05 to -0.56; P < 0.0001)), fasting plasma glucose (-1.6 mmol/L (95% CI: -2.49 to -0.63; P = 0.0017)) and body weight (-2.6 kg (95% CI: -3.68 to -1.55; P < 0.0001)). In insulin-experienced patients, the mean total daily insulin dose did not change significantly (estimated change from baseline to EOS 3.8 (95% CI: -3.70 to 11.21; P = 0.3202)). The proportion of patients experiencing hypoglycaemia numerically decreased during the study (non-severe: 14.2-10.9%; nocturnal non-severe: 4.9-2.2%; and severe: 2.2-0%).
CONCLUSIONS: Initiating or switching to IDegAsp in a real-world population of people with T2D in Australia was associated with significant improvements in glycaemic control and body weight, and numerically lower levels of hypoglycaemia compared with baseline.

OBJECTIVE: This study aimed to investigate the effects of glycaemic control and diabetes distress on frailty in older Chinese patients with diabetes, and to explore the mediating role of diabetes distress between glycaemic control and frailty.
METHODS: This is a descriptive, cross-sectional study. A total of 209 older patients with diabetes were recruited from a teaching hospital in Zhejiang Province. Data were collected from February to September 2022.
METHODS: A self-designed questionnaire was used to collect demographic and disease-related data. The Fried Scale and Diabetes Distress Scale were employed to assess frailty and diabetes distress, respectively The bootstrap method was used to examine the mediating effects of diabetes distress on glycaemic control and frailty. The STROBE checklist was adhered to in the reporting of this study (see details in File S1).
RESULTS: The findings indicated a positive correlation between the level of glycaemic control and frailty, as well as between diabetes distress and frailty. Furthermore, diabetes distress was found to play a complete mediating role between glycaemic control and frailty.
CONCLUSIONS: The study findings highlight the relationship between glycaemic control, diabetes distress and frailty offering a valuable reference for enhancing the management of frailty in older patients with diabetes.
CONCLUSIONS: This study emphasizes the significance of managing glycaemic control and diabetes distress in older patients with diabetes to prevent frailty, and may contribute for healthcare professionals to developing effective measures to improve the frailty of older diabetic patients in clinical settings.
UNASSIGNED: This study was conducted with the participation of older patients with diabetes who contributed data by completing study questionnaires and undergoing physical assessments.

A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes.