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AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is common in people with type 2 diabetes (T2D) and can progress to advanced fibrosis and cirrhosis. In this retrospective study, we explored the longitudinal changes in markers of hepatic steatosis and fibrosis during T2D treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS: We analysed observational data from six diabetes outpatient clinics. In the whole T2D population, we calculated the hepatic steatosis index (HSI), which we previously validated against liver ultrasonography, and the Fibrosis (Fib)-4 index. We then identified patients who initiated a GLP-1RA from 2010 to 2018 and for whom data were available to evaluate changes in both HSI and Fib-4 scores over 24 months. RESULTS: From 83,116 outpatients with T2D, 41,302 (49.7%) had complete data for calculating HSI and Fib-4. Most of these T2D patients (â¼70%) had MAFLD (defined as HSI>36), 9.7% of whom had advanced fibrosis based on Fib-4 thresholds. Patients with low compared to high risk of advanced fibrosis were 5-times more likely to be treated with GLP-1RA. In 535 patients who initiated a GLP-1RA, the prevalence of MAFLD based on HSI declined significantly at 6 and 24 months, but Fib-4 categories did not. HSI improved significantly only in patients receiving human-based but not exendin-based GLP-1RA, while patients concomitantly receiving metformin had less worsening in Fib-4 categories. CONCLUSIONS: MAFLD is very common among outpatients with T2D (â¼70%) and the estimated prevalence of advanced fibrosis was â¼10%. Treatment with GLP-1RAs significantly improved MAFLD, but not MAFLD-associated advanced fibrosis.
Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Liver Cirrhosis , Biomarkers , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors , Glucagon-Like Peptide-1 Receptor/therapeutic use , Humans , Liver Cirrhosis/diagnosis , Longitudinal Studies , Retrospective StudiesABSTRACT
AIMS: We evaluated de-intensification of basal-bolus insulin (BBI) after initiation of a GLP-1 receptor agonist (GLP-1RA) under routine care. RESEARCH DESIGN AND METHODS: This retrospective, multicenter study conducted at outpatient clinics in North-East Italy collected data on patients with T2D on BBI who initiated a GLP-1RA. Patients were divided according to whether they de-intensified BBI at the end of observation by stopping prandial insulin. RESULTS: We included 425 patients with mean age of 61.3 years and 13 years of diabetes duration. Baseline HbA1c was 8.6% and BMI was 35.5 kg/m2. After 14 months. 58.6% of patients de-intensified BBI after initiating GLP-1RA: they were younger, had a shorter disease duration, lower HbA1c and insulin dose, and less frequent microangiopathy than those who continued BBI. A probability estimation based on these variables was validated in an independent cohort of 40 patients. Body weight improved in both groups, but HbA1c and fasting plasma glucose significantly declined only among patients who de-intensified BBI. Patients who de-intensified BBI and persisted on GLP-1RA at the last observation (80.7%) had greater HbA1c reductions. CONCLUSION: Under routine care, GLP-1RA initiation frequently allowed discontinuing BBI, especially among patients with shorter disease duration, lower insulin requirement, and better glucose control.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/therapeutic use , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Female , Humans , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Male , Middle Aged , Retrospective StudiesABSTRACT
INTRODUCTION: Combination therapy with both basal insulin (BI) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is an effective treatment in patients with uncontrolled type 2 diabetes mellitus (T2DM). The recent development and release of a fixed-ratio combination of slow-release insulin degludec and the GLP-1RA liraglutide (IDegLira) represents an improvement to this therapy. We have conducted a real-world evidence study in Italian patients with T2DM to evaluate whether the encouraging clinical trial results obtained with IDegLira, which became available in Italy in January 2018, can be confirmed in Italian clinical practice. METHODS: This was a multicenter, retrospective, observational study in patients with T2DM treated with IDegLira from January to December 2018. Prior to the initiation of IDegLira therapy, patients were treated with BI with or without one or more concomitant oral antidiabetic drugs (BOT group) or according to the basal bolus protocol (BI and rapid-acting insulin treatment; BB group). RESULTS: A total of 244 patients were included in the present study, of whom 186 were in the BOT group and 58 in the BB group. Following the switch to IDegLira therapy, glycemic control improved in both groups, with significant reductions in glycated hemoglobin after 6 and 12 months of treatment in the BOT group and after 6 months of treatment in the BB group. No gain in body weight and body mass index and reductions in fasting plasma glucose and number of concomitant diabetic medications (in BOT patients) were observed. All results obtained during the study were achieved at a moderate dose of IDegLira. CONCLUSION: The findings from this study show that in a real-world setting, the switch to IDegLira treatment is a valid option for patients who are failing to achieve glycemic control targets and/or struggling with the side effects, such as weight gain and hypoglycemia, of other insulin therapies.
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CONTEXT: In randomized controlled trials (RCTs) on type 2 diabetes (T2D) patients, the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-RA) dulaglutide reduced HbA1c and body weight, but generalizability of such findings to real-world T2D patients is challenging. OBJECTIVE: We evaluated effectiveness of dulaglutide in routine clinical practice, especially in subgroups of patient that are underrepresented in RCTs. DESIGN: Retrospective multicenter study. SETTING: Diabetes outpatient clinics. PATIENTS AND INTERVENTION: All consecutive patients who initiated dulaglutide between 2015 and 2018. MAIN OUTCOME MEASURES: Changes in HbA1c and body weight were assessed up to 30 months after baseline. Effectiveness was analyzed in patient subgroups according to: prior use of GLP-1RA, persistence on treatment and dose, age, sex, disease duration, renal function, obesity, cardiovascular disease, or concomitant use of insulin or sulphonylurea. RESULTS: From a background population of 83,116 patients, 2084 initiated dulaglutide (15.3% switching from another GLP-1RA), 1307 of whom had at least 1 follow-up visit. Overall, dulaglutide reduced HbA1c by 1.0% and body weight by 2.9 kg at the end of observation. These effects were more pronounced in GLP-1RA-naïve patients and in those with shorter disease duration. Improvement in HbA1c was highly significant and consistent across all subgroups, including those aged ≥ 75 years, nonobese, or with chronic kidney disease. Body weight declined in all subgroups and significantly more with the 1.5-mg versus 0.75-mg dose. CONCLUSIONS: In real-world T2D patients, effectiveness of dulaglutide on HbA1c and body weight reduction was highly consistent and significant even in subgroups of patients poorly represented in RCTs.
Subject(s)
Body Weight/drug effects , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptides/analogs & derivatives , Hypoglycemic Agents/therapeutic use , Immunoglobulin Fc Fragments/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Weight Loss/drug effects , Aged , Blood Glucose , Diabetes Mellitus, Type 2/blood , Female , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/therapeutic use , Glycated Hemoglobin , Humans , Hypoglycemic Agents/administration & dosage , Immunoglobulin Fc Fragments/administration & dosage , Male , Middle Aged , Recombinant Fusion Proteins/administration & dosage , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION AND AIM: Real-word data on the head-to-head comparisons among glucagon-like peptide-1 receptor agonists (GLP-1RA) are scant. Therefore, we aimed to compare the effectiveness of dulaglutide versus liraglutide and exenatide once weekly (exeOW) in type 2 diabetic (T2D) patients under routine care. METHODS: This was a retrospective, multicenter, real-world study on patients with T2D (aged 18-80) initiating a GLP-1RA between 2010 and 2018 at specialist outpatient clinics. We compared the effectiveness of dulaglutide versus liraglutide and exeOW on the changes in HbA1c (primary outcome), body weight, blood pressure and fasting glucose (secondary outcomes). Average follow-up was 5.9â¯months. Channelling biases were addressed with propensity score matching or multivariable adjustment. Meta-analyses of observational studies, covering the same comparisons, are also presented. RESULTS: 849, 1371 and 198 patients were included in the dulaglutide, liraglutide and exeOW groups, respectively. The reduction of HbA1c was greater with dulaglutide than with liraglutide (-0.24⯱â¯0.08%; pâ¯=â¯0.003), and was confirmed in the meta-analysis of observational studies. In our study, dulaglutide showed similar effectiveness compared to exeOW. When these results were pooled with other observational studies, dulaglutide showed a greater reduction of HbA1c (-0.19%; pâ¯=â¯0.003) and body weight (-0.8â¯kg; pâ¯=â¯0.007). CONCLUSIONS: In a real-world scenario, dulaglutide reduced HbA1c more than liraglutide. Conversely, we found similar effect of dulaglutide and exeOW, with statistical differences arising solely when results were meta-analysed with those from other observational studies. Lack of up-titration for liraglutide and higher discontinuation rate for exeOW likely influenced the estimated treatment difference.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Exenatide/administration & dosage , Glucagon-Like Peptides/analogs & derivatives , Immunoglobulin Fc Fragments/administration & dosage , Liraglutide/administration & dosage , Observational Studies as Topic/statistics & numerical data , Recombinant Fusion Proteins/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Drug Administration Schedule , Drug Therapy, Combination , Exenatide/adverse effects , Female , Follow-Up Studies , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/adverse effects , Humans , Immunoglobulin Fc Fragments/adverse effects , Liraglutide/adverse effects , Male , Middle Aged , Recombinant Fusion Proteins/adverse effects , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
AIMS: Several GLP-1 receptor agonists (GLP-1RA) have become available for the treatment of type 2 diabetes (T2D), and evidence on their beneficial effects has evolved. We evaluated how the clinical phenotype of patients initiating GLP-1RA changed from 2010 to 2018. METHODS: This was a retrospective study conducted at six diabetes outpatient clinics in Northeast Italy. We collected data of T2D patients who initiated new GLP-1RA between 2010 and 2018. We recorded baseline characteristics, including demographics, anthropometrics, cardiovascular risk factors, glucose control, lipid profile, liver enzymes, renal function and concomitant medications. We recorded updated HbA1c and body weight at follow-up. RESULTS: There were 83,116 T2D patients from a general population of ~ 1,380,000 inhabitants. Among 6167 cases of GLP-1RA initiation, 5408 were analyzed after excluding intra-class switchers. Prescription of GLP-1RA increased exponentially, and the change in the type of GLP-1RA reflected waves of their entering the market. From 2010 to 2018, there were significant increases in baseline age, diabetes duration and prevalence of male sex, of cardiovascular disease and of insulin users. Blood pressure and cholesterol levels decreased concomitantly with increasing use of medications for the control of cardiovascular risk. Baseline average HbA1c (8.3% [67 mmol/mol]) and BMI (34 kg/m2) and their improvement after GLP-1RA initiation did not change over time. CONCLUSIONS: Despite the early positioning of GLP-1RA in T2D treatment algorithms, GLP-1RA have been prescribed in patients with progressively more advanced disease stage and especially in the presence of cardiovascular disease. Optimization of GLP-1RA use in routine clinical practice is still needed.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/administration & dosage , Aged , Blood Glucose/metabolism , Blood Pressure , Body Mass Index , Body Weight , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Female , Glycated Hemoglobin/metabolism , Humans , Italy/epidemiology , Lipids/blood , Male , Middle Aged , Prevalence , Retrospective StudiesABSTRACT
BACKGROUND AND AIMS: The combination of basal insulin (BI) and GLP-1 receptor agonists (GLP-1RAs) is a rational and effective therapy for patients with uncontrolled type 2 diabetes (T2D). We compared the effectiveness of fixed and flexible BI/GLP-1RA combinations using routinely accumulated clinical data. METHODS: This was a retrospective, multicentre, real-world study concerning T2D patients initiating a fixed or flexible BI/GLP-1RA combination (NCT03959865). The primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight, fasting plasma glucose (FPG) and systolic blood pressure (SBP). Confounding was addressed by propensity score matching (PSM) or multivariable adjustment (MVA). RESULTS: A total of 609 patients were included in the study, 131 in the fixed group and 478 in the flexible group. The two groups differed in terms of diabetes duration, body weight and concomitant medications. After 5.7 months, observed HbA1c reductions were 0.6% and 0.8%, and body weight reductions were 2.8 kg and 1.2 kg in the flexible and fixed groups, respectively. Following PSM, HbA1c declined similarly in the two groups, whereas reduction in body weight was significantly in favour of the flexible combination. Findings were robust in sensitivity analyses, with the exception that, with MVA, a significantly higher reduction in HbA1c was detected in the fixed group. Final doses of BI were higher in the fixed group, whereas those of GLP-1RA were higher in the flexible group. CONCLUSIONS: In routine specialist care, initiation of the fixed or flexible BI/GLP-1RA combination allowed similar improvement in glycaemic control, but greater weight loss was observed with the flexible combination. This difference reflected dosages of BI and GLP-1RAs.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Aged , Blood Glucose , Drug Therapy, Combination , Female , Glucagon-Like Peptide-1 Receptor/administration & dosage , Glycated Hemoglobin , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Male , Middle Aged , Retrospective StudiesABSTRACT
Background Evidence accumulated that some glucose-lowering medications protect against cardiovascular events ( CVEs ) in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. The present study evaluated if and how glucose-lowering medication prescription pattern changes in T2DM after a CVE. Methods and Results DATAFILE (Diabetes Therapy After a Cardiovascular Event) was a retrospective multicenter study conducted at 12 diabetes mellitus specialist outpatient clinics in Italy. We identified T2DM patients with an incident CVE for whom a follow-up visit was available after the event. We selected control T2DM patients without an incident CVE , who were matched with cases for age, sex, known diabetes mellitus duration, baseline hemoglobin A1c, kidney function, and follow-up time. We extracted clinical variables and compared prescribed therapies at baseline and follow-up. We included 563 patients with and 497 matched patients without an incident CVE . As expected, patients with a subsequent CVE had a higher baseline prevalence of ischemic heart disease. After a median of 9.5 months, in patients with versus those without a CVE , there was a significant increase in the prescription of beta-blockers, loop diuretics, dual antiplatelet therapy, and, among glucose-lowering medications, a significant decrease in metformin. Hemoglobin A1c marginally declined only in the control group, whereas low-density lipoprotein cholesterol decreased only in patients with CVE . Conclusions This study highlights that occurrence of a CVE in T2DM patients did not prime the prescription of glucose-lowering medications provided with cardiovascular protective effects, even though glucose control remained poor. These data emphasize the need to optimize the therapeutic regimen of T2DM patients with established cardiovascular disease, according to updated guidelines.
Subject(s)
Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardiovascular Diseases/complications , Cholesterol, LDL , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Dual Anti-Platelet Therapy , Female , Glycated Hemoglobin/metabolism , Heart Failure/complications , Heart Failure/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Italy , Male , Metformin/therapeutic use , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Myocardial Ischemia/complications , Myocardial Ischemia/drug therapy , Myocardial Revascularization , Sodium Potassium Chloride Symporter Inhibitors/therapeutic useABSTRACT
In this study, we retrospectively compared the effectiveness of exenatide once-weekly (ExeOW) versus liraglutide in non-insulin treated patients with type 2 diabetes followed under routine care. We also present a meta-analysis of similar observational studies available in the literature. In our multicentre retrospective study, patients initiating ExeOW (n = 204) or liraglutide (n = 410) had similar baseline clinical characteristics. Change in HbA1c at 6 months was superimposable in the two groups (-0.7% ± 1.0%), and changes in body weight were also similar (ExeOW -2.2 ± 3.7 kg; liraglutide -2.5 ± 4.3 kg; p = 0.457). Discontinuation rates were numerically but not significantly lower for ExeOW versus liraglutide. Pooling these data with those of observational studies available in the literature yielded superimposable effects between the two groups for the change in HbA1c and body weight, with a higher risk of discontinuation (mainly based on pharmacy refill rates) for ExeOW. We conclude that, in patients under routine care, initiation of ExeOW provides similar benefits on HbA1c and body weight as initiation of liraglutide. These data help view the results of randomized controlled trials from the perspective of their application in routine clinical practice.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Exenatide/administration & dosage , Liraglutide/administration & dosage , Adult , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Drug Administration Schedule , Female , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/administration & dosage , Male , Observational Studies as Topic/statistics & numerical data , Primary Health Care/statistics & numerical data , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Based on existing data regarding the durability of liraglutide in type 2 diabetes, this study aimed to assess its long-term effectiveness at 5 years and its overall impact on cardiovascular (CV) risk. METHODS: This was a multicenter retrospective observational study. Liraglutide was used under routine clinical practice conditions. Changes from baseline to 60 months in HbA1c, fasting plasma glucose (FPG), body weight, blood pressure, and lipid profile were assessed. United Kingdom Prospective Diabetes Study (UKPDS) scores were calculated at baseline and after 60 months to assess changes in the estimated 5- and 10-year risk for fatal and nonfatal coronary heart disease (CHD) and fatal and nonfatal stroke. RESULTS: Overall, 103 patients (age 59.0 ± 7.9 years, diabetes duration 10.4 ± 6.8 years) were involved in the study. After 60 months, HbA1c levels were reduced by - 1.0 ± 1.2%, FPG levels by - 24.5 ± 43.4 mg/dl, body weight by - 5.3 ± 6.4 kg, systolic blood pressure by - 6.5 ± 18.5 mmHg, diastolic blood pressure by - 3.6 ± 11.8 mmHg, and total cholesterol by - 16.9 ± 37.4 mg/dl. The proportion of patients achieving HbA1c levels of < 7% increased from 12.7% to 39.8% (p = 0.02). Based on the UKPDS scores, statistically significant reductions in the 5- and 10-year risk of nonfatal CHD and fatal CHD were found, with no change in the 5- and 10-year risk of fatal and nonfatal stroke. CONCLUSION: In patients prolonging treatment with liraglutide for 5 years, the benefits in relation to metabolic control and CV risk factors are maintained. The UKPDS risk scores suggest that liraglutide is associated with a reduced CHD risk, but not with a reduced stroke risk.
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INTRODUCTION: The aim of the study was to evaluate whether the reduction in glycated hemoglobin (HbA1c) observed in clinical trials with liraglutide in type 2 diabetes (T2D) could be attained in routine clinical practice. METHODS: ReaL was a multicenter, non-interventional, observational, retrospective, longitudinal study on the effectiveness of liraglutide, a human glucagon-like peptide-1 analog, in individuals with T2D treated in daily practice in Italy. Between 26 March and 16 November 2015, data were taken from clinical records of patients aged ≥ 18 years with treatment follow-up data of up to 24 months and who received their first prescription of liraglutide in 2011. RESULTS: A total of 1723 patients were included in the analysis. At baseline, mean age was 58.9 years, duration of diabetes was 9.6 years, and HbA1c was 8.3%. At 12 months, 36.1% of patients were prescribed the maximum 1.8 mg dose; 43.5% [95% confidence interval (CI): 40.9; 46.2] of patients attained the primary outcome of a reduction in HbA1c of ≥ 1% point at 12 months. At 24 months, 40.9% (95% CI 38.1; 43.7) of patients had attained the HbA1c target of ≤ 7%. Additionally, body weight significantly decreased by 3.4 kg (95% CI - 3.6; - 3.1, p < 0.0001). CONCLUSION: In this observational study conducted in routine clinical practice for up to 2 years, treatment with liraglutide improved HbA1c and reduced body weight in a similar fashion to that observed under randomized clinical trial conditions. The data support the use of liraglutide as an effective treatment for T2D in clinical practice. FUNDING: Novo Nordisk S.p.A. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02255266.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Adult , Aged , Body Weight/drug effects , Female , Glycated Hemoglobin/analysis , Humans , Italy , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: To assess the efficacy and safety of insulin degludec administered in a basal-bolus regimen according to the GesTIO protocol in noncritical hospitalized patients with T1DM and T2DM. METHODS: Mean blood glucose levels (BG) and their standard deviations (SD) at admission vs. discharge were compared in 52 subjects (48.1% ≥75 years) managed through a basal-bolus scheme including degludec. The percentages of patients with BG at target (140-180 mg/dl) or below at discharge and the incidence rate (and the 95% confidence interval for it) of hypoglycemia were assessed. RESULTS: From admission to discharge, fasting BG decreased from 237 to 153 mg/dl (p < 0.0001) and SD dropped from 125 to 38 mg/dl (p < 0.0001); average BG decreased from 189 to 145 mg/dl (SD dropped from 57 to 32 mg/dl). At discharge, 28.9% had BG at target, while 50.0% had lower levels (average 119.0 ± 14.4 mg/dl). The incidence rate of hypoglycemia was 0.07 (0.05; 0.11) episodes per person-day; 1 out of 27 episodes occurred during the night. CONCLUSIONS: Degludec in hospitalized, mainly elderly patients is effective and minimizes glucose variability and nocturnal hypoglycemia.
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PURPOSE: Treatment with liraglutide in randomized controlled trials is associated with significant reductions in glycated hemoglobin (HbA1c) and weight loss in type 2 diabetes patients. The aim of this retrospective observational study was to investigate correlations of glycemic control and weight outcomes with baseline characteristics of patients starting liraglutide in outpatient clinics in Italy. METHODS: Type 2 diabetes patients were followed from baseline to 4, 8, and 12 months. Changes in glycemic parameters, weight, blood pressure, and lipids were assessed. Subanalyses were performed according to baseline characteristics. Multivariate linear and logistic regressions were used to assess correlations between glycemic efficacy, weight reduction, and liraglutide discontinuation after 12 months and baseline characteristics. FINDINGS: Four hundred and eighty-one patients were included. Mean (SD) age at baseline was 57.3 (9.2) years, diabetes duration was 9.5 (6.8) years, weight was 106.7 (20.8) kg, body mass index (BMI; calculated as kg/m(2)) was 37.1 (6.6), HbA1c was 8.7% (1.3%), fasting plasma glucose was 168.5 (45.3) mg/dL; 38.2% were treated previously with insulin and 52.2% were treated with metformin alone. After 12 months, mean (SD) changes were HbA1c -1.2% (1.4%), fasting plasma glucose -28.3 (41.1) mg/dL, weight -3.5 (5.8) kg, BMI -1.3 (2.1), waist circumference -2.6 (6.7) cm (all, P < 0.001). Drop in weight and HbA1c did not differ between baseline BMI classes ≤30 or >30. Weight loss was unchanged among diabetes duration quartiles, and HbA1c reduction was significantly greater in patients with ≤4 years of diabetes duration (P = 0.01). Non-insulin-treated patients reached HbA1c ≤7% significantly more often than treated patients (44.2% vs 21.2%; odds ratio = 2.94; P < 0.001) and had significantly greater weight loss (-4.5 [8.2] kg vs -2.6 [5.4] kg; P = 0.03). Patients on metformin reached HbA1c target more frequently than others (43.1% vs 29.7%; odds ratio = 1.80; 95% CI, 1.05-3.07). Significant positive determinants for HbA1c reduction after 12 months were baseline HbA1c, age, and prior metformin monotherapy, and weight loss at 12 months was positively correlated with baseline weight, and negatively correlated with prior insulin treatment. Overall, 5.0% of patients interrupted liraglutide before the 12th month due to lack of glycemic control; they were less frequently treated with metformin only before liraglutide (29.2% vs 50.2%; P = 0.04). IMPLICATIONS: Treatment with liraglutide in a real-world setting is associated with low therapy failure, good glycemic response, weight loss, and improvement in systolic blood pressure and lipid profile. The HbA1c drop did not differ among baseline BMI classes, indicating that efficacy is maintained in patients with lower BMI. The probability of reaching HbA1c ≤7% was significantly higher in patients previously treated with metformin alone and without any previous insulin. This could reinforce the hypothesis that better results with liraglutide could be achieved in patients after early metformin failure.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Metformin/therapeutic use , Aged , Blood Glucose/drug effects , Body Mass Index , Body Weight , Female , Glycated Hemoglobin/analysis , Humans , Insulin/therapeutic use , Italy , Lipids/blood , Male , Middle Aged , Retrospective StudiesABSTRACT
The GLP-1 receptor agonist Liraglutide is effective in reducing HbA1c in type 2 diabetic (T2D) patients. In addition, treatment with Liraglutide is associated with significant weight loss. In this study, we analyzed the inter-relationships between glycemic and weight effects of Liraglutide treatment in a population of type 2 diabetic outpatients. T2D patients initiating Liraglutide therapy since September 2010 to July 2012 at 3 outpatient clinics were enrolled and followed-up. We collected baseline information about anthropometric data, cardiovascular risk factors, diabetes duration, prevalence of complications and history of anti-diabetic medications. We collected HbA1c and body weight at baseline and every 4 months. A total of 166 patients were included, who were on average 56.6 ± 8.9 (mean ± SD) years old and had a baseline HbA1c of 8.7 ± 1.3 % and BMI 36.3 ± 6.4 kg/m(2). Mean follow-up was 9.4 ± 4.2 months (range 4-16). Patients lost on average 1.5 ± 1.3 % HbA1c and 4.0 ± 5.0 kg body weight. Most patients (73.5 %) improved HbA1c and loosed weight. Significant independent determinants of HbA1c drop were baseline HbA1c (r = 0.673; p < 0.001) and previous insulin therapy (r = -0.251; p < 0.001). The only independent determinant of weight loss was baseline BMI (r = 0.429; p < 0.001). Drop in HbA1c was unrelated to baseline BMI or weight loss. Weight loss was unrelated to baseline HbA1c or drop in HbA1c. Glycemic improvement and weight reduction obtained with Liraglutide treatment in T2D patients in a real-world setting are independent and possibly mediated by different mechanisms.