Metabolic dysfunction-associated steatotic liver disease and atherosclerosis.

PURPOSE OF REVIEW: To update information about the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis. This review emphasizes the potential mechanisms linking MASLD with atherosclerosis and the possible causal relationships between these conditions. RECENT FINDINGS: An increased risk of cardiovascular disease is related to MASLD. Several molecular, cellular, and metabolic mechanisms have been described to explain the development of atherothrombosis in MASLD patients. These include atherogenic dyslipidemia, low-grade vascular inflammation, endothelial dysfunction, foam cell formation, proliferation of vascular smooth muscle cells, insulin resistance, gut microbiota dysbiosis, activation of renin-angiotensin and sympathetic nervous systems, hypercoagulability, and decreased fibrinolysis. Also, there is recent evidence suggesting an association between genetically driven liver fat and coronary heart disease mediated by the causal effect of apoB-containing lipoproteins. Several meta-analyses and systematic reviews have reported a strong association between MASLD and cardiovascular outcomes. MASLD is an important and independent risk factor for atherosclerosis development. Multiple mechanisms may be involved in this association. Further research is required to establish a causal association between MASLD and atherosclerosis.

Type 1 Diabetes Care in Mexico: An Analysis of the RENACED-DT1 National Registry.

BACKGROUND: Information regarding diagnosis, treatment, and follow-up of patients with type 1 diabetes (PWT1D) in Mexico is limited. We developed an on-line platform Registro Nacional de Pacientes con Diabetes Tipo 1 (RENACED-DT1). OBJECTIVE: The objective of the study was to describe the characteristics and healthcare of PWT1D registered in RENACED-DT1. METHODS: Analyses of 965 PWT1D from July 2014 to January 2018 in different endocrinology clinics around Mexico. RESULTS: Sixty-one percent were female with median age of 21 years, age at diagnosis 11 years, and disease duration at inclusion 8.2 years. Treatment regimen was basal-bolus in 61% and insulin-pumps in 21% (mainly in the private sector); 33.3% with self-monitoring of blood-glucose (SMBG) ≥4 times/day. Mean HbA1c at last follow-up was 8.7 ± 2.1% (72±23 mmol/mol), 18% had HbA1c < 7% (53 mmol/mol), and 35% > 9% (75 mmol/mol). SMBG ≥ 4 times/day was associated with HbA1c < 7%. Time since diagnosis > 10 years, female sex, BMI ≥ 30 kg/m2, SMBG < 4 times/day, and any hypoglycemia were associated with microvascular complications (p < 0.05). CONCLUSIONS: Percentage of patients achieving HbA1c < 7% is low; increased blood glucose monitoring is associated with better glycemic control. The achievement of optimal glycemic control must be increased to reduce the incidence of chronic complications and improve quality of life in PWT1D.

Efficacy and safety of dual add-on therapy with dapagliflozin plus saxagliptin versus glimepiride in patients with poorly controlled type 2 diabetes on a stable dose of metformin: Results from a 52-week, randomized, active-controlled trial.

AIMS: To evaluate the efficacy and safety of dapagliflozin (DAPA) + saxagliptin (SAXA) compared with glimepiride (GLIM) in patients with type 2 diabetes who were inadequately controlled [glycated haemoglobin (HbA1c) 7.5-10.5% (58-91 mmol/mol)] on metformin monotherapy. MATERIALS AND METHODS: This 52-week, multicentre, double-blind, active-controlled study (NCT02419612) randomized (1:1) patients on metformin to add-on DAPA 10 mg + SAXA 5 mg (n = 227) or GLIM 1-6 mg (titrated; n = 217). The primary efficacy endpoint was change in HbA1c from baseline to week 52. RESULTS: Baseline mean ± standard deviation of age, duration of diabetes and HbA1c were 56.1 ± 9.7 years, 7.8 ± 6.4 years and 8.5% ± 0.8% (69 ± 9.0 mmol/mol), respectively. Adjusted mean change from baseline in HbA1c was -1.35% (-14.8 mmol/mol) with DAPA + SAXA versus -0.98% (-10.7 mmol/mol) with GLIM (P <0.001). Changes from baseline in body weight and systolic blood pressure were -3.1 kg and -2.6 mmHg with DAPA + SAXA versus +1.0 kg (P <0.001) and +1.0 mmHg (P = 0.007) with GLIM. More patients achieved HbA1c <7.0% (53 mmol/mol) (44.3% vs. 34.3%; P = 0.044), and fewer patients required treatment intensification (1.3% vs. 8.8%; P = 0.002) with DAPA + SAXA than with GLIM. CONCLUSIONS: Compared with GLIM, concurrent addition of DAPA + SAXA significantly improved glycaemic control, body weight and other metabolic parameters in patients inadequately controlled on metformin. Trial: NCT02419612, ClinicalTrials.gov.

VASCULAR COMPLICATIONS IN PATIENTS WITH TYPE 2 DIABETES: PREVALENCE AND COMORBIDITIES IN 6 COUNTRIES OF LATIN AMERICA (A COHORT OF THE DISCOVER STUDY PROGRAM).

Objective: To provide real world observational data about glucose control, the burden of diabetes, comorbidities, and cardiovascular risk factors among patients initiating second-line therapy in Latin America (LA). Methods: This report is a cross-sectional analysis of the LA cohort of the DISCOVER study, describing the regional prevalence of microvascular and macrovascular complications in Mexico, Costa Rica, Panama, Colombia, Argentina, and Brazil. Results: One thousand six hundred and sixteen patients were included in 69 investigational sites. Hemoglobin A1c was >7% (42 mmol/mol) in 81.3% of subjects. Macrovascular complications were reported by 13.8% of the subjects. Microvascular conditions were reported in 15.2% of the subjects. The prevalence of hypertension and of hyperlipidemia was 55.5% and 45.9%, respectively. Blood pressure, total cholesterol, and low-density lipoprotein were out of target levels in 38.5%, 51.2%, and 81.7% of the patients, respectively. Overweight or obesity was reported in 83.8% of the cases. Conclusion: Our study shows that patients with type 2 diabetes in LA are not reaching their glucose, lipids, blood pressure, and weight targets. The prevalence of microvascular (15.2%), macrovascular (13.8%), and uncontrolled comorbidities in patients at an early stage of the disease (initiating a second-line therapy) highlights the need for more aggressive risk factor screening as well as treatment in LA. Abbreviations: CV = cardiovascular; CVD = cardiovascular disease; DM = diabetes mellitus; HbA1c = hemoglobin A1c; LA = Latin America/Latin American; LDL = low density cholesterol; T2DM = type 2 diabetes mellitus.

A cross-sectional study on the prevalence of cardiovascular disease in elderly patients with long-term type 2 diabetes mellitus mainly attended in private clinics in Mexico. The CAPTURE study.

BACKGROUND: To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico. METHODS: CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study. RESULTS: Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1-39.6] and 29.5% [26.7-32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6-25-7], 8.4% [6.8-10.0], 5.0% [3.5-6.5] and 3.9% [2.6-5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively. CONCLUSIONS: In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit.

Glycemic Control and Prevention of Diabetic Complications in Low- and Middle-Income Countries: An Expert Opinion.

INTRODUCTION: Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking. METHODS: This is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015-2016) and the GOAL study conducted in multiple LMICs. RESULTS: Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c [HbA1c] ≥ 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5-12 and > 12 years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5-12 years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duration 10.1 ± 6.7 years; 10 LMIC). A significant 2% reduction in mean HbA1c levels was observed after 12 months of treatment. Only 7.2% of participants experienced a symptomatic episode of hypoglycemia (nocturnal or severe hypoglycemia events were infrequent). CONCLUSION: The rate of well-controlled participants (HbA1c < 7.0%) in the Wave 7 sub-analysis was lower than that observed in the USA (NHANES survey) or in European countries (GUIDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients' education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.

Glycemic control, treatment and complications in patients with type 1 diabetes amongst healthcare settings in Mexico.

AIMS: Type 1 diabetes (T1D) is a growing chronic disease. Evidence of whether the healthcare setting affects management and glycemic control is scarce. We evaluate outcomes in patients with T1D in private and public healthcare settings in Mexico, registered in the National T1D Registry in Mexico (RENACED-DT1). METHODS: Biochemical parameters, diabetes education, and treatment were analyzed considering the data registered in the last visit. Development of chronic complications was determined during follow-up. RESULTS: We included 1,603 patients; 71.5% (n = 1,146) registered in the public system, and 28.5% (n = 457) in a private institution. Patients in the public setting had higher HbA1c (8.6%, IQR: 7.3%-10.5% vs 7.7%, IQR: 7.0%-8.8%; p < 0.001). Indicators of diabetes education, glucose monitoring, and use of insulin-pumps were lower in the public setting. Patients in the public setting were at higher risk of diabetic chronic kidney disease, retinopathy, and neuropathy. Diabetes knowledge was a mediator between type of healthcare setting and the likelihood of achieving glycemic control. CONCLUSIONS: Patients registered in public healthcare settings have an adverse metabolic profile and higher risk of complications. Social factors need to be addressed in order to implement multidisciplinary measures focused on diabetes education for patients with T1D in Mexico.

[Liraglutide and glimepiride on glycaemic control in type 2 diabetes in the Mexican cohort (LEAD 3)]. / Liraglutida y glimepirida para el control glucémico de la diabetes tipo 2. Análisis de la cohorte mexicana de LEAD-3.

OBJECTIVE: To compare the efficacy of liraglutide monotherapy with glimepiride monotherapy in subjects with DM2 inadequately controlled by previous treatment of diet/exercise or oral antidiabetic drug. METHODS: A 52-week, double-blinded, active-controlled, parallel-group, multi-centre, prospective trial, involving 746 subjects was conducted in the USA and Mexico. In Mexico, 171 subjects were rando-mised (1:1:1) to once daily liraglutide (either 1.2, or 1.8 mg/day injected subcutaneously) or glimepiride (8 mg/day orally). RESULTS: Hb1Ac reduced by 0.64%, 1.31% and 0.30% with glimepiride, liraglutide 1.8 mg and 1.2 mg, respectively. Body weight decreased with both liraglutide doses while a weight gain of 0.94 kg was observed with glimepiride. FPG reduced by 27.9 mg/dL with liraglutide 1.8 mg, whereas a FPG increase of 9.54 mg/dL was shown with glimepiride. No major hypoglycaemic episodes were reported in this trial. CONCLUSIONS: in Mexican subjects with DM2, liraglutide monotherapy can provide greater reduction in HbA1c, weight loss and lower risk of hypoglycaemia in comparison with glimepiride.

Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes (DUAL VIII): a multicentre, open-label, phase 3b, randomised controlled trial.

BACKGROUND: Durability of glycaemic control might reduce disease burden and improve long-term outcomes. DUAL VIII investigated the durability of insulin degludec plus liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) in patients with type 2 diabetes with the use of a visit schedule that mirrored routine clinical practice. METHODS: In this 104-week international, multicentre, open-label, phase 3b randomised controlled trial, insulin-naive patients aged 18 years and older, with HbA1c between 7·0-11·0% (53-97 mmol/mol), BMI of 20 kg/m2 or higher, on stable doses of oral antidiabetic drugs, were recruited from outpatient clinics. Patients were randomly assigned 1:1, with a simple sequential allocation randomisation schedule (block size of four), to IDegLira or IGlar U100, each treatment being an add-on to existing therapy. The internal safety committee, the independent external committee, and the personnel involved in defining the analysis sets were masked until the database was released for statistical analysis. Patients and all other investigators were not masked. In the IDegLira group, patients were given degludec 100 units/mL plus liraglutide 3·6 mg/mL in a 3 mL prefilled PDS290 pen for subcutaneous injection; in the IGlar U100 group, patients were given IGlar U100 solution, in a 3 mL prefilled Solostar pen for subcutaneous injection. Both treatments were given once daily at any time of day and it was recommended that the time of day remained the same throughout the trial. The primary endpoint was time from randomisation to need for treatment intensification (HbA1c ≥7·0% [53 mmol/mol] at two consecutive visits, including week 26). Once patients met this criterion, the trial product was permanently discontinued and patients were not withdrawn from trial but rather remained on follow-up for the entire treatment and follow-up period. The primary analysis was in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02501161. FINDINGS: From Jan 8, 2016, to Oct 3, 2018, 1345 patients were screened, of which 1012 (75·2%) were eligible and randomly assigned to either IDegLira (n=506) or IGlar U100 (n=506). 484 (96%) of 506 in the IDegLira group and 481 (95%) of 506 in the IGlar U100 group completed the trial. Baseline characteristics were similar and representative of patients eligible for basal insulin intensification (overall mean diabetes duration 10 years; HbA1c 8·5% [69 mmol/mol]; fasting plasma glucose 10 mmol/L). Patients in the IDegLira group had significantly longer time until intensification was needed than those in the IGlar U100 group (median >2 years vs about 1 year). Fewer patients in the IDegLira group needed treatment intensification over 104 weeks than those in the IGlar U100 group (189 [37%] of 506 vs 335 [66%] of 506). The preplanned sensitivity analyses of the primary endpoint were in agreement with the primary analysis (hazard ratio 0·45 [95% CI 0·38-0·54]) in the proportional hazards regression model and the generalised log-rank test was also in favour of IDegLira (p<0·0001). No new or unexpected safety and tolerability issues were identified and there were no treatment-related deaths. INTERPRETATION: In patients with uncontrolled type 2 diabetes on oral antidiabetic drugs, initial injectable therapy with IDegLira resulted in fewer patients reaching the treatment intensification criterion during 104 weeks versus IGlar U100, with longer durability of the treatment effect with IDegLira. FUNDING: Novo Nordisk.

Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension.

OBJECTIVE: To evaluate efficacy and safety of 60mg and 120mg Fimasartan (FMS) alone or combined with 12.5mg hydrochlorothiazide (HCTZ) in a Mexican population. METHODS: A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90mmHg were randomised to either 120mg FMS or 60mg FMS + 12.5mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90mmHg received 120mg FMS+12.5mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. RESULTS: FMS 60mg (n=272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3±8.9 (p<.0001) and 16.0±14.1 (p<.0001)mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120mg, FMS 60mg+HCTZ 12.5mg, or FMS 120mg+HCTZ 12.5mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP<90mmHg and an SBP<140mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). CONCLUSION: Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.

Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial.

OBJECTIVE: This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. RESEARCH DESIGN AND METHODS: After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA1c levels at 30 weeks. RESULTS: HbA1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1c from baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c <7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi. CONCLUSIONS: Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes.

Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse ß-cell function in the GetGoal-M and GetGoal-S trials.

AIMS: To evaluate the impact of ß-cell function on the efficacy of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this post hoc analysis, patients from the Phase 3 GetGoal-M and GetGoal-S clinical trials randomized to lixisenatide 20µg once daily were stratified into quartiles by baseline ß-cell function, as measured by the secretory units of islet in transplantation (SUIT) index. RESULTS: Patients (N=437) were distributed evenly among SUIT index quartiles 1 to 4 (lowest to highest ß-cell function). Clinical outcomes improved from baseline across all SUIT quartiles; mean changes at week 24 were: glycated hemoglobin (HbA1c; % [mmol/mol]), -0.99 (-10.8), -0.87 (-9.5), -0.86 (-9.4), -0.83 (-9.1); and postprandial plasma glucose (PPG; mmol/L), -7.9, -5.6, -5.5, -4.3 (overall effect P<0.0001). Furthermore, postprandial glucagon was reduced in all SUIT quartiles, while insulinogenic index improved only in patients with higher baseline SUIT (overall effect P=0.0286). No severe symptomatic hypoglycemic events were reported. CONCLUSIONS: Lixisenatide treatment resulted in reductions in HbA1c and PPG levels across all SUIT quartiles. This suggests that non-insulin-related actions of lixisenatide contribute to improved glycemic control in T2D.

Type 1 diabetes care in mexico: an analysis of the renaced-dt1 national registry

Background: Information regarding diagnosis, treatment, and follow-up of patients with type 1 diabetes (PWT1D) in Mexico is limited. We developed an on-line platform Registro Nacional de Pacientes con Diabetes Tipo 1 (RENACED-DT1). Objective: The objective of the study was to describe the characteristics and healthcare of PWT1D registered in RENACED-DT1. Methods: Analyses of 965 PWT1D from July 2014 to January 2018 in different endocrinology clinics around Mexico. Results: Sixty-one percent were female with median age of 21 years, age at diagnosis 11 years, and disease duration at inclusion 8.2 years. Treatment regimen was basal-bolus in 61% and insulin-pumps in 21% (mainly in the private sector); 33.3% with self-monitoring of blood-glucose (SMBG) ≥4 times/day. Mean HbA1c at last follow-up was 8.7 ± 2.1% (72±23 mmol/mol), 18% had HbA1c < 7% (53 mmol/mol), and 35% > 9% (75 mmol/mol). SMBG ≥ 4 times/day was associated with HbA1c < 7%. Time since diagnosis > 10 years, female sex, BMI ≥ 30 kg/m2, SMBG < 4 times/day, and any hypoglycemia were associated with microvascular complications (p < 0.05). Conclusions: Percentage of patients achieving HbA1c < 7% is low; increased blood glucose monitoring is associated with better glycemic control. The achievement of optimal glycemic control must be increased to reduce the incidence of chronic complications and improve quality of life in PWT1D.

Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, parallel-group trial.

BACKGROUND: Pioglitazone and glimepiride improve glycemic control in patients with type 2 diabetes mellitus by different mechanisms. Pioglitazone is a thiazolidinedione that reduces insulin resistance, and glimepiride is a sulfonylurea insulin secretagogue. OBJECTIVE: The goals of this study were to compare changes in measures of glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes who received pioglitazone or glimepiride for 1 year. METHODS: This was a multicenter, 52-week, double-blind, parallel-group trial. Patients were randomized to receive monotherapy with either glimepiride (2 mg QD initially) or pioglitazone (15 mg QD initially). Doses were titrated (maximal doses: pioglitazone 45 mg, glimepiride 8 mg) to achieve glycemic targets (fasting blood glucose < or =7 mmol/L and 1-hour postprandial blood glucose < or =10 mmol/L). Insulin sensitivity (primary end point) was evaluated in terms of the Homeostasis Model Assessment for Insulin Sensitivity (HOMA-S), the Quantitative Insulin Sensitivity Check Index (QUICKI), and fasting serum insulin (FSI) concentrations. Glycemic control was evaluated in terms of glycosylated hemoglobin (HbA(1c)) values and fasting plasma glucose (FPG) concentrations. Patients were encouraged to maintain their individual diet and exercise regimens throughout the study. RESULTS: Two hundred forty-four patients (125 women, 119 men; all but 1 Hispanic) were randomized to receive pioglitazone (n = 121) or glimepiride (n = 123). In the intent-to-treat sample, pioglitazone and glimepirede produced comparable reductions in HbA(1c) from baseline to the end of the study (-0.78% and -0.68%, respectively). The pioglitazone group had significantly higher HbA(1c) values compared with the glimepiride group after 12 weeks of therapy (8.66% vs 7.80%; P = 0.007) but had significantly lower values after 52 weeks (7.46% vs 7.77%; P = 0.027). Pioglitazone significantly reduced FPG compared with glimepiride (-0.6 vs 0.6 mmol/L; P = 0.01). Pioglitazone therapy was associated with significant increases in insulin sensitivity (reduced insulin resistance), whereas glimepiride had no effect. HOMA-S values changed 18.0% for pioglitazone and -7.9% for glimepiride (P < 0.001), QUICKI values changed a respective 0.013 and -0.007 (P < 0.001), and FSI values were -21.1 and 15.1 pmol/L (P< 0.001). Both drugs were well tolerated, with pioglitazone associated with more peripheral edema (number of treatment-emergent cases: 35/121[28.9%] vs 17/123 [13.8%]; P = 0.005) and fewer hypoglycemic episodes (19 [15.7%] vs 38 [30.9%]; P = 0.024). The incidence of weight gain was not significantly different between treatment groups. CONCLUSIONS: These data suggest that long-term treatment with pioglitazone enhances insulin sensitivity relative to glimepiride in Mexican patients with type 2 diabetes and that pioglitazone may have a more sustained antihyperglycemic effect.

Type 2 diabetes mellitus management and body mass index: experiences with initiating insulin detemir in the a1chieve study.

INTRODUCTION: This sub-analysis of the A1chieve study aimed to examine the safety and efficacy of insulin detemir (IDet) initiation over 24 weeks in relation to baseline body mass index (BMI) in people with type 2 diabetes mellitus (T2DM). METHODS: A1chieve was a 24-week non-interventional study to assess the safety and efficacy of insulin analogs in routine practice. This sub-analysis included insulin-naïve patients who initiated IDet therapy based on their physicians' decision. Patients were stratified according to baseline BMI (Group I, <25.0 kg/m(2); Group II, 25.0 to <30.0 kg/m(2); Group III, 30.0 to <35.0 kg/m(2); Group IV ≥35.0 kg/m(2)). Safety and efficacy variables were assessed over 24 weeks. RESULTS: Overall, 10,650 insulin-naïve patients were included (3,045 patients in Group I, 4,186 patients in Group II, 2,365 patients in Group III, and 1,054 patients in Group IV). Four serious adverse drug reactions (SADRs) were reported. From baseline to Week 24, there was no statistically significant difference in the proportion of patients reporting overall hypoglycemia in Group I (4.0% vs. 4.4%), while a significant decrease in Group II (4.8% vs. 4.0%, p = 0.0335) and significant increases in Groups III and IV (3.3% vs. 5.4% and 3.4% vs. 7.0%, respectively, p < 0.001) were noted. The mean body weight increased from baseline to Week 24 in Group I (60.7 ± 8.4 vs. 61.8 ± 8.5 kg) and reduced in Groups II, III, and IV (74.5 ± 9.2 vs. 74.2 ± 9.2 kg, 87.4 ± 10.3 vs. 86.0 ± 9.8 kg, and 102.2 ± 14.3 vs. 100.1 ± 14.2 kg, respectively; all p < 0.001). Significant improvements were noted in glycemic parameters, systolic blood pressure, and lipids over 24 weeks, irrespective of baseline BMI status. CONCLUSION: IDet therapy was associated with improved glycemic control and a low number of SADRs. Greater weight loss was observed with higher BMI.

Predictive and explanatory factors of change in HbA1c in a 24-week observational study of 66,726 people with type 2 diabetes starting insulin analogs.

OBJECTIVE: Individualization of therapy choices requires the prediction of likely response. Predictor and explanatory factors of change in HbA1c were studied using data from a large observational study of starting insulin analog therapy (the A1chieve study). RESEARCH DESIGN AND METHODS: Univariate analyses were performed for insulin-naive people and prior insulin users in the A1chieve study. Statistically significant factors were carried forward to baseline factor-only multivariate analyses ("predictor" analysis), and separately using all significant factors ("explanatory" analysis). Power was considered in terms of the variance explained. RESULTS: Geographical region, baseline HbA1c level, lipid levels, and baseline insulin dose were the most powerful predictors of HbA1c change (mean change -2.1% [-23 mmol/mol]) observed in the univariate analysis (r2 > 0.010, P < 0.001). However, although the predictor and explanatory multivariate models explained 62-82% of the variance in HbA1c change, this was mainly associated with baseline HbA1c (r2 = 0.544-0.701) and region (r2 = 0.014-0.037). Other factors were statistically significant but had low predictive power (r2 < 0.010); in the explanatory analysis, this included end-of-study hypoglycemia (insulin-naive group), insulin dose, and health-related quality of life (r(2) < 0.001-0.006, P ≤ 0.007). CONCLUSIONS: Many factors can guide clinicians in predicting the response to starting therapy with insulin analogs, but many are interdependent and thus of poor utility. The factor explaining most of the variance in HbA1c change is baseline HbA1c level, with each increase of 1.0%-units (11 mmol/mol) providing a 0.7-0.8%-units (8-9 mmol/mol) greater fall. Other factors do not explain much of the remaining variance, even when including all end-of-trial measures.

The effectiveness and safety of beginning insulin aspart together with basal insulin in people with type 2 diabetes in non-Western nations: results from the A1chieve observational study.

AIMS: The aim of this A1chieve sub-group analysis was to examine populations beginning insulin aspart together with any basal insulin, all ± oral glucose lowering drugs: insulin aspart added to existing basal insulin (n=519); switched from biphasic insulin (n=947); switched from NPH plus human meal-time insulins (n=586); and insulin-naïve begun with basal plus insulin aspart (n=1594). METHODS: A1chieve was a 24-week non-interventional study evaluating insulin analogues in 66,726 people with type 2 diabetes in routine clinical care in 28 non-Western countries. Major endpoints were analysed as change from baseline using Student's paired t-test. RESULTS: Baseline glycaemic control was poor (mean HbA1c: 9.4-10.1% [79-87 mmol/mol]). HbA1c, FPG and PPPG improved significantly from baseline in all groups (mean change from baseline in HbA1c: -2.8 to -1.8% [-31 to -20 mmol/mol]; FPG: -4.9 to -2.9 mmol/L; PPPG: -6.7 to -3.9 mmol/L; p<0.001 for all), resulting in a similar level of blood glucose control for all groups at study end. Unsurprisingly, hypoglycaemia rates increased in those starting insulin, but decreased in the other groups. Clinically significant improvements in serum lipids and quality of life occurred across all groups. CONCLUSIONS: These data support the use of basal plus prandial insulin regimens in routine clinical practice in people with type 2 diabetes with inadequate glycaemic control.

Safety and effectiveness of insulin detemir in different age-groups in the a1chieve study.

INTRODUCTION: Diabetes therapy should balance glycemic control with risk of adverse events. This sub-analysis of the A1chieve study evaluated clinical safety and effectiveness of insulin detemir in different age-groups (≤40 years, >40-65 years, and >65 years) of insulin-experienced and insulin-naïve people with type 2 diabetes. METHODS: A1chieve was an international, open-label, non-interventional, 24-week study in 66,726 people with type 2 diabetes starting/switching to therapy with biphasic insulin aspart 30, insulin detemir or insulin aspart (alone/in combination) in routine clinical practice. This sub-analysis evaluated clinical safety and effectiveness in patients starting/switching to insulin detemir (±oral glucose-lowering drugs). RESULTS: In total, 15,241 patients were included in the sub-analysis. In all age-groups, the proportion of participants experiencing any, major or nocturnal hypoglycemia was significantly (all p < 0.05) reduced relative to baseline, except in insulin-naïve patients for any and nocturnal hypoglycemia, where there was a significant increase or no significant change in patients aged >65 years and >40-65 years, respectively, and no significant change in major hypoglycemia in insulin-naïve patients aged ≤40 years. Seven serious adverse drug reactions were reported. Body weight was significantly reduced in patients aged ≤40 years and >40-65 years and significantly increased in insulin-naïve patients aged >65 years at 24 weeks. At 24 weeks, glycated hemoglobin was reduced by 2.3%, 2.0%, and 1.8%, in the ≤40 years, >40-65 years, and >65 years age-groups, respectively (all p < 0.001). Fasting and post-prandial plasma glucose were significantly reduced and health-related quality of life (HRQoL) significantly improved across all patient cohorts (all p < 0.001). CONCLUSION: After 24-week treatment with insulin detemir, all age-groups of insulin-experienced and insulin-naïve patients had significantly improved glycemic control and HRQoL. The proportion of patients experiencing hypoglycemia was reduced in all age-groups but unchanged in insulin-naïve patients aged >40-65 years and increased in insulin-naïve patients aged >65 years. The safety and effectiveness of insulin detemir may benefit all age-groups.