This document summarizes the results of a study comparing exenatide once weekly (QW) plus metformin to placebo plus metformin in patients with type 2 diabetes. Key findings include:
- Treatment with exenatide QW significantly reduced glycemic fluctuations compared to placebo, as measured by reductions in distance traveled and total energy of daily glucose levels.
- Energy spectrum analysis showed the reductions in energy with exenatide QW were mainly in slower glucose changes rather than fast changes.
- The effects of exenatide QW on 24-hour glucose levels depended on patient age and baseline glucose, with greater reductions seen in those with higher baseline glucose levels.
This randomized controlled trial evaluated the effects of exenatide once weekly (QW) compared to placebo on glycemic control in patients with type 2 diabetes already taking metformin. Over 10 weeks:
1) Exenatide QW significantly reduced 24-hour mean glucose levels, fasting plasma glucose, post-prandial glucose, and glucose fluctuations compared to placebo.
2) Exenatide QW significantly increased the amount of time patients spent in the target glycemic range without increasing hypoglycemia.
3) Glycemic control improvements with exenatide QW were seen as early as 4 weeks and continued to week 10, demonstrating a robust and sustained response.
From Pregnancy to Menopause: Studies of Physical Activity, Behavior, and Ener...InsideScientific
Join Sharon Ladyman, PhD and Vicki Vieira-Potter, PhD as they present applications of rodent metabolic phenotyping with a focus on the effects of hormones and pregnancy on daily activity in mice.
A reduction in voluntary physical activity during pregnancy in mice is mediated by prolactin
Sharon Ladyman, PhD
Pregnancy is an energetically demanding challenge for the mother and as such, pregnant females undergo numerous metabolic adaptations to meet these demands, including increased food intake and a rapid lowering of energy expenditure and physical activity levels. A particularly striking example is a profound reduction in voluntary running wheel activity (RWA) that occurs as soon as mice become pregnant. We hypothesized that prolactin, one of the first hormones to increase in response to mating in rodents, drives the pregnancy-induced suppression of physical activity levels.
Neuronal and Metabolic Pathways Influenced by Sex Hormones
Vicki Vieira-Potter, PhD
Estrogen-sufficient females are more physically active than males and are protected against adipose tissue and systemic metabolic dysfunction. The mechanisms are not fully understood, but we demonstrate that ovarian removal causes significant mRNA changes in the nucleus accumbens (NAc) brain region (i.e., the reward center), which correlate significantly with physical inactivity. We hypothesize that sex differences in the NAc may help explain differences in physical activity and metabolism.
Resultados del estudio DEVOTE (Devote 1-2-3): Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at HighRisk of Cardiovascular Events
Ponencia realizada por el Dr. Eduard Montanya Mias del Hospital Universitari de Bellvitge (Barcelona). Director Científico CIBERDEM en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
The document contains demographic and baseline characteristic data from the DEVOTE clinical trial comparing insulin degludec to insulin glargine in patients with type 2 diabetes at high risk for cardiovascular events. A total of 7637 patients from 20 countries across 5 continents were enrolled in the trial. At baseline, the mean age was approximately 65 years for both treatment groups. Slightly over 60% of patients were male. Patients had a mean duration of diabetes of approximately 16 years and the majority (over 84%) had established cardiovascular or chronic kidney disease and were aged 50 years or older.
Ponencia en Congreso ASCARICA (Tenerife 23 feb 18) sobre Riesgo CV DM2 y GLP1. Aplicaciones clínicas practicas derivadas de los estudios de seguridad CV de los fármacos para la DM2
Imeglimin a new class a new approach for diabetes management yara eid
1. Mitochondrial dysfunction plays a key role in the pathogenesis of type 2 diabetes through decreased oxidative capacity, increased reactive oxygen species production, and impaired insulin secretion.
2. Imeglimin is a new antidiabetic drug that targets mitochondrial function through several mechanisms, including improving complex II activity, decreasing oxidative stress, and increasing PGC-1α and mitochondrial biogenesis.
3. Clinical trials have shown imeglimin to be effective at reducing blood glucose levels and to have a good safety profile, suggesting it may be a promising new treatment for type 2 diabetes.
This randomized controlled trial evaluated the effects of exenatide once weekly (QW) compared to placebo on glycemic control in patients with type 2 diabetes already taking metformin. Over 10 weeks:
1) Exenatide QW significantly reduced 24-hour mean glucose levels, fasting plasma glucose, post-prandial glucose, and glucose fluctuations compared to placebo.
2) Exenatide QW significantly increased the amount of time patients spent in the target glycemic range without increasing hypoglycemia.
3) Glycemic control improvements with exenatide QW were seen as early as 4 weeks and continued to week 10, demonstrating a robust and sustained response.
From Pregnancy to Menopause: Studies of Physical Activity, Behavior, and Ener...InsideScientific
Join Sharon Ladyman, PhD and Vicki Vieira-Potter, PhD as they present applications of rodent metabolic phenotyping with a focus on the effects of hormones and pregnancy on daily activity in mice.
A reduction in voluntary physical activity during pregnancy in mice is mediated by prolactin
Sharon Ladyman, PhD
Pregnancy is an energetically demanding challenge for the mother and as such, pregnant females undergo numerous metabolic adaptations to meet these demands, including increased food intake and a rapid lowering of energy expenditure and physical activity levels. A particularly striking example is a profound reduction in voluntary running wheel activity (RWA) that occurs as soon as mice become pregnant. We hypothesized that prolactin, one of the first hormones to increase in response to mating in rodents, drives the pregnancy-induced suppression of physical activity levels.
Neuronal and Metabolic Pathways Influenced by Sex Hormones
Vicki Vieira-Potter, PhD
Estrogen-sufficient females are more physically active than males and are protected against adipose tissue and systemic metabolic dysfunction. The mechanisms are not fully understood, but we demonstrate that ovarian removal causes significant mRNA changes in the nucleus accumbens (NAc) brain region (i.e., the reward center), which correlate significantly with physical inactivity. We hypothesize that sex differences in the NAc may help explain differences in physical activity and metabolism.
Resultados del estudio DEVOTE (Devote 1-2-3): Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at HighRisk of Cardiovascular Events
Ponencia realizada por el Dr. Eduard Montanya Mias del Hospital Universitari de Bellvitge (Barcelona). Director Científico CIBERDEM en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
The document contains demographic and baseline characteristic data from the DEVOTE clinical trial comparing insulin degludec to insulin glargine in patients with type 2 diabetes at high risk for cardiovascular events. A total of 7637 patients from 20 countries across 5 continents were enrolled in the trial. At baseline, the mean age was approximately 65 years for both treatment groups. Slightly over 60% of patients were male. Patients had a mean duration of diabetes of approximately 16 years and the majority (over 84%) had established cardiovascular or chronic kidney disease and were aged 50 years or older.
Ponencia en Congreso ASCARICA (Tenerife 23 feb 18) sobre Riesgo CV DM2 y GLP1. Aplicaciones clínicas practicas derivadas de los estudios de seguridad CV de los fármacos para la DM2
Imeglimin a new class a new approach for diabetes management yara eid
1. Mitochondrial dysfunction plays a key role in the pathogenesis of type 2 diabetes through decreased oxidative capacity, increased reactive oxygen species production, and impaired insulin secretion.
2. Imeglimin is a new antidiabetic drug that targets mitochondrial function through several mechanisms, including improving complex II activity, decreasing oxidative stress, and increasing PGC-1α and mitochondrial biogenesis.
3. Clinical trials have shown imeglimin to be effective at reducing blood glucose levels and to have a good safety profile, suggesting it may be a promising new treatment for type 2 diabetes.
This study examines urinary N-acetyl β-D-glucosaminidase (NAG) as an early biomarker for detecting renal tubular damage in type 2 diabetes mellitus patients at risk for diabetic nephropathy. 991 patients were divided into 8 groups based on diabetes status and duration, albuminuria levels, and presence of nephropathy. Urinary and serum NAG levels increased with longer diabetes duration and worsening albuminuria/nephropathy. A urinary NAG cutoff of 3 U/L differentiated patients with 10+ years of diabetes, microalbuminuria, and nephropathy from controls, with high specificity and sensitivity. The study concludes urinary NAG can
The document is a program for a conference on the treatment of heart failure in patients with comorbidities. It includes the following sessions:
1. Chronic Kidney Disease. RAAS inhibitors are not an option.
2. The patient with heart failure and atrial fibrillation.
3. Addressing obesity: why, when and how to intervene?
4. Dyslipidemia and heart failure. Any changes with the new guidelines?
ЭФФЕКТИВНОСТЬ ОПРЕДЕЛЕНИЯ АКТИВНОСТИ N-АЦЕТИЛ БЕТА- D- ГЛЮКОЗАМИНИДАЗЫ В МОЧЕ...sergeykulchitskiy5
1. The study evaluated urinary N-acetyl β-D-glucosaminidase (NAG) as an early diagnostic biomarker for diabetic nephropathy in type 2 diabetes mellitus patients.
2. A cutoff value of 3 U/L for urinary NAG differentiated patients with 10-15 years and 15-20 years of diabetes, microalbuminuria, and diabetic nephropathy from controls with high specificity and sensitivity.
3. Increased urinary NAG excretion correlated with longer diabetes duration and higher microalbumin levels, indicating it is a site-specific marker of early tubular damage from long-term hyperglycemia.
Door Prof. Dr. Hans Bijlsma wordt ingegaan op de balans tussen effectiviteit en veiligheid bij Glucocorticoїden (GC): leiden GC altijd tot botverlies, of kan het ontstekingsremmend effect sterker zijn dan de direct negatieve effecten op het bot? Zijn de bijwerkingen dosis-afhankelijk? Hoe kijken patiënten tegen bijwerkingen aan? Zijn er nieuwe medicamenten in aantocht met minder bijwerkingen?
Dr Emma Ridley is a senior research fellow and ICU dietitian who has published extensively in the field of nutrition. She discloses research funding from Baxter Healthcare and having received speaking fees from them. Her top 5 publications focus on characterizing the metabolic phenotype during critical illness, investigating the effects of very high protein enteral nutrition, examining how pre-existing kidney function impacts outcomes with IV amino acid supplementation, comparing enteral versus parenteral nutrition in shock patients, and a large trial investigating energy-dense versus routine enteral nutrition.
The document summarizes studies on the use of SGLT2 inhibitors in patients with type 1 diabetes. A 18-week study of canagliflozin in 351 patients with type 1 diabetes found reductions in HbA1c of 0.29% and 0.25% for the 100mg and 300mg doses respectively, along with weight reductions of 2.8kg and 4.4kg. Insulin doses were also reduced. Hypoglycemia rates were similar between groups. A study of sotagliflozin found reductions of 0.46% in HbA1c, 2.98kg in weight, 3.5mmHg in blood pressure, and 5.25 units in insulin dose. Two larger
C19 nice dapagliflozin in combination therapy for treating type2 diabetes 2013Diabetes for all
The document summarizes evidence submitted by manufacturers on the clinical effectiveness of dapagliflozin for treating type 2 diabetes. Trials showed dapagliflozin combined with metformin reduced HbA1c and body weight more than placebo. Compared to sulfonylureas, dapagliflozin achieved non-inferior HbA1c reductions with less hypoglycemia and greater weight loss. Dapagliflozin combined with insulin reduced HbA1c, weight, blood pressure and insulin dose more than placebo. Network meta-analyses found dapagliflozin reduced HbA1c versus placebo and reduced weight more than some comparators.
Continuous Glucose Monitoring and Its Use Beyond Type 1 DiabetesAaron Neinstein
This document discusses the potential for continuous glucose monitor (CGM) use beyond just type 1 diabetes. It begins by predicting that by 2025, everyone with diabetes will be using CGMs and many without diabetes will also be tracking their blood sugar. It then reviews the evidence that CGMs improve outcomes for those with type 2 diabetes compared to fingerstick monitoring alone. Several studies show CGMs lower A1c and time spent in hypoglycemia. The document also discusses emerging data on using CGMs in those without known diabetes to identify patterns of glucose dysregulation. It concludes that while interest in broader CGM use is growing, many questions remain around defining optimal populations, dosing, and care models to support non-diabetic
5. Frank Buttgereit. Fin40 min rheumatic diseases and osteoporosiscrea-autoinmunidad
This document discusses secondary osteoporosis, glucocorticoid-induced osteoporosis, and emerging drugs for osteoporosis. It summarizes recent findings on the relationship between bone mass and atherosclerosis in systemic lupus erythematosus patients. It also discusses the high prevalence of osteoporosis in ankylosing spondylitis patients and recommendations for assessing osteoporosis in these patients. Finally, it reviews glucocorticoid use and comorbidities in giant cell arteritis patients and the contribution of both disease and glucocorticoid treatment to osteoporosis risk in these patients.
This study examined whether metformin use predicts prostate cancer diagnosis and prognosis. 1034 men underwent transperineal template-guided mapping biopsy and were divided into 3 groups: nondiabetic, diabetic not taking metformin, diabetic taking metformin. Metformin did not predict cancer diagnosis or severity. Univariate and multivariate analyses found only age predicted cancer diagnosis, and age, PSA velocity, and BMI predicted higher Gleason scores (≥7). While metformin may reduce cancer risk in other types based on biochemical pathways, prostate cancer cells' fast doubling time may limit metformin's effects. Larger studies in more diverse populations are needed to better understand metformin's role in prostate cancer.
Abdulmoein Al-Agha discusses the use of insulin degludec in managing pediatric diabetes. Insulin degludec is an ultra-long acting basal insulin that provides over 42 hours of basal insulin coverage and achieves similar glycemic control to insulin glargine with less overnight hypoglycemia. Insulin degludec has a half-life of approximately 25 hours, double that of insulin glargine. It also has significantly less day-to-day variability in glucose-lowering effect compared to insulin glargine. These properties allow for more flexibility in dosing time compared to other basal insulins.
This document summarizes research on the effects of alternative hormonal treatments, including bazedoxifene, on various tissues in humans. It discusses preclinical and clinical data on the effects of ospemifene, tamoxifen, raloxifene, and bazedoxifene on the endometrium, vagina, breast, and bone. It then summarizes results from several clinical trials, known as the SMART trials, that evaluated the efficacy and safety of a combination of conjugated estrogens and bazedoxifene for vasomotor symptoms, quality of life, vaginal health, and bone mineral density and fracture risk reduction.
This document summarizes results from the AURA-LV clinical trial studying the efficacy and safety of voclosporin in treating lupus nephritis. The trial found that patients receiving 23.7 mg of voclosporin twice daily were over twice as likely to achieve complete renal remission at 24 weeks compared to the placebo group. They were also more likely to achieve partial remission and saw faster time to response. At 48 weeks, the low-dose voclosporin group maintained higher remission rates and saw continued improvement in proteinuria levels over time, demonstrating voclosporin's potential as a new treatment for lupus nephritis.
This clinical note discusses a patient's diabetes management. It notes low blood sugar symptoms during the night and pain/oozing from surgical wounds. It provides guidance on following the diabetes diet, exercise/medication plan, monitoring blood sugar levels, maintaining proper oral hygiene due to infection risk, and foot care. Concerns about blood sugar control and emotional state are also mentioned.
SGLT2 Inhibitors v Sitagliptin (SITA) as Add-on Therapy to Metformin Chris Sevald, PhD
SGLT2 inhibitors are the latest class of FDA-approved oral therapies to lower blood glucose in type-2 diabetes.Systematic review and meta-analysis to compare glucose-lowering and weight-loss effects of SGLT2s vs. the most-prescribed DPP-4 inhibitor, SITA. Poster presented at the 21st annual meeting of ISPOR, May, 2016, in Washington DC.
Fine Tuning Nutrient Intake Timing for Cardiac HealthInsideScientific
Cardiovascular function changes on a daily basis with potential implications for risk of heart attack and sudden cardiac death. In this webinar, Martin Young, DPhil, will discuss these cardiovascular changes and the potential mechanisms that govern these 24-hour rhythms with a particular focus on circadian clocks. These studies highlight that circadian clocks modulate processes that are critical for normal cardiovascular function, including metabolism. Daily rhythms in metabolism, in turn, influence the manner with which organs (such as the heart) respond to nutrient intake. Dr. Young illustrates the concept that the time of day at which specific macronutrients (such as lipids and proteins) are consumed dramatically impacts the heart. Dr. Young showcases the relevance of these basic science findings to human population studies.
Statins are highly effective LDL-c lowering agents that actually reduce clinical cardiovascular events. The 2013 ACC/AHA guidelines on the management of blood cholesterol recommend high-intensity statin therapy in individuals with high cardiovascular risk as assessed by the 10-year atherosclerotic cardiovascular disease risk calculator. However, a significant number of individuals do not tolerate or respond adequately to statins, and continue to have residual risk in spite of high intensity statin therapy.
There are some exciting developments in the field of lipidology. This decade has been labeled “The PCSK9 decade”. A new class of monoclonal antibodies directed against the PCSK9 glycoproteins appears very promising in further lowering LDL cholesterol and thereby cardiovascular risk. Evolocumab and alirucomab are novel PCSK9 inhibitors that can be given subcutaneously once or twice in a month, and have the potential to reduce LDL-cholesterol to very low levels without any major adverse effects.
Other classes of drugs like Apo-B antisense oligonucleotides (mipomersen), CETP inhibitors (especially anacetrapib), microsomal transfer protein inhibitors (lomitapide) also hold some promise. The future of lipid lowering therapy looks reassuring with these new developments.
Shashikiran Umakanth presented this at the Egyptian Association of Endocrinology, Diabetes & Atherosclerosis (EAEDA) 2014 conference at Alexandria, Egypt. This conference was help in association with Endocrine Society, USA and the European Association for the Study of Diabetes (EASD).
This document provides an overview of canagliflozin, an SGLT2 inhibitor used to treat type 2 diabetes. It discusses the pathogenesis of type 2 diabetes, progressive beta cell dysfunction, and the kidney's role in glucose regulation. It then reviews canagliflozin's mechanism of action as an SGLT2 inhibitor, increasing urinary glucose excretion and reducing blood glucose levels. The document summarizes canagliflozin's clinical trials, pharmacokinetics, efficacy, safety profile, and effects on renal function and lipids.
This study examines urinary N-acetyl β-D-glucosaminidase (NAG) as an early biomarker for detecting renal tubular damage in type 2 diabetes mellitus patients at risk for diabetic nephropathy. 991 patients were divided into 8 groups based on diabetes status and duration, albuminuria levels, and presence of nephropathy. Urinary and serum NAG levels increased with longer diabetes duration and worsening albuminuria/nephropathy. A urinary NAG cutoff of 3 U/L differentiated patients with 10+ years of diabetes, microalbuminuria, and nephropathy from controls, with high specificity and sensitivity. The study concludes urinary NAG can
The document is a program for a conference on the treatment of heart failure in patients with comorbidities. It includes the following sessions:
1. Chronic Kidney Disease. RAAS inhibitors are not an option.
2. The patient with heart failure and atrial fibrillation.
3. Addressing obesity: why, when and how to intervene?
4. Dyslipidemia and heart failure. Any changes with the new guidelines?
ЭФФЕКТИВНОСТЬ ОПРЕДЕЛЕНИЯ АКТИВНОСТИ N-АЦЕТИЛ БЕТА- D- ГЛЮКОЗАМИНИДАЗЫ В МОЧЕ...sergeykulchitskiy5
1. The study evaluated urinary N-acetyl β-D-glucosaminidase (NAG) as an early diagnostic biomarker for diabetic nephropathy in type 2 diabetes mellitus patients.
2. A cutoff value of 3 U/L for urinary NAG differentiated patients with 10-15 years and 15-20 years of diabetes, microalbuminuria, and diabetic nephropathy from controls with high specificity and sensitivity.
3. Increased urinary NAG excretion correlated with longer diabetes duration and higher microalbumin levels, indicating it is a site-specific marker of early tubular damage from long-term hyperglycemia.
Door Prof. Dr. Hans Bijlsma wordt ingegaan op de balans tussen effectiviteit en veiligheid bij Glucocorticoїden (GC): leiden GC altijd tot botverlies, of kan het ontstekingsremmend effect sterker zijn dan de direct negatieve effecten op het bot? Zijn de bijwerkingen dosis-afhankelijk? Hoe kijken patiënten tegen bijwerkingen aan? Zijn er nieuwe medicamenten in aantocht met minder bijwerkingen?
Dr Emma Ridley is a senior research fellow and ICU dietitian who has published extensively in the field of nutrition. She discloses research funding from Baxter Healthcare and having received speaking fees from them. Her top 5 publications focus on characterizing the metabolic phenotype during critical illness, investigating the effects of very high protein enteral nutrition, examining how pre-existing kidney function impacts outcomes with IV amino acid supplementation, comparing enteral versus parenteral nutrition in shock patients, and a large trial investigating energy-dense versus routine enteral nutrition.
The document summarizes studies on the use of SGLT2 inhibitors in patients with type 1 diabetes. A 18-week study of canagliflozin in 351 patients with type 1 diabetes found reductions in HbA1c of 0.29% and 0.25% for the 100mg and 300mg doses respectively, along with weight reductions of 2.8kg and 4.4kg. Insulin doses were also reduced. Hypoglycemia rates were similar between groups. A study of sotagliflozin found reductions of 0.46% in HbA1c, 2.98kg in weight, 3.5mmHg in blood pressure, and 5.25 units in insulin dose. Two larger
C19 nice dapagliflozin in combination therapy for treating type2 diabetes 2013Diabetes for all
The document summarizes evidence submitted by manufacturers on the clinical effectiveness of dapagliflozin for treating type 2 diabetes. Trials showed dapagliflozin combined with metformin reduced HbA1c and body weight more than placebo. Compared to sulfonylureas, dapagliflozin achieved non-inferior HbA1c reductions with less hypoglycemia and greater weight loss. Dapagliflozin combined with insulin reduced HbA1c, weight, blood pressure and insulin dose more than placebo. Network meta-analyses found dapagliflozin reduced HbA1c versus placebo and reduced weight more than some comparators.
Continuous Glucose Monitoring and Its Use Beyond Type 1 DiabetesAaron Neinstein
This document discusses the potential for continuous glucose monitor (CGM) use beyond just type 1 diabetes. It begins by predicting that by 2025, everyone with diabetes will be using CGMs and many without diabetes will also be tracking their blood sugar. It then reviews the evidence that CGMs improve outcomes for those with type 2 diabetes compared to fingerstick monitoring alone. Several studies show CGMs lower A1c and time spent in hypoglycemia. The document also discusses emerging data on using CGMs in those without known diabetes to identify patterns of glucose dysregulation. It concludes that while interest in broader CGM use is growing, many questions remain around defining optimal populations, dosing, and care models to support non-diabetic
5. Frank Buttgereit. Fin40 min rheumatic diseases and osteoporosiscrea-autoinmunidad
This document discusses secondary osteoporosis, glucocorticoid-induced osteoporosis, and emerging drugs for osteoporosis. It summarizes recent findings on the relationship between bone mass and atherosclerosis in systemic lupus erythematosus patients. It also discusses the high prevalence of osteoporosis in ankylosing spondylitis patients and recommendations for assessing osteoporosis in these patients. Finally, it reviews glucocorticoid use and comorbidities in giant cell arteritis patients and the contribution of both disease and glucocorticoid treatment to osteoporosis risk in these patients.
This study examined whether metformin use predicts prostate cancer diagnosis and prognosis. 1034 men underwent transperineal template-guided mapping biopsy and were divided into 3 groups: nondiabetic, diabetic not taking metformin, diabetic taking metformin. Metformin did not predict cancer diagnosis or severity. Univariate and multivariate analyses found only age predicted cancer diagnosis, and age, PSA velocity, and BMI predicted higher Gleason scores (≥7). While metformin may reduce cancer risk in other types based on biochemical pathways, prostate cancer cells' fast doubling time may limit metformin's effects. Larger studies in more diverse populations are needed to better understand metformin's role in prostate cancer.
Abdulmoein Al-Agha discusses the use of insulin degludec in managing pediatric diabetes. Insulin degludec is an ultra-long acting basal insulin that provides over 42 hours of basal insulin coverage and achieves similar glycemic control to insulin glargine with less overnight hypoglycemia. Insulin degludec has a half-life of approximately 25 hours, double that of insulin glargine. It also has significantly less day-to-day variability in glucose-lowering effect compared to insulin glargine. These properties allow for more flexibility in dosing time compared to other basal insulins.
This document summarizes research on the effects of alternative hormonal treatments, including bazedoxifene, on various tissues in humans. It discusses preclinical and clinical data on the effects of ospemifene, tamoxifen, raloxifene, and bazedoxifene on the endometrium, vagina, breast, and bone. It then summarizes results from several clinical trials, known as the SMART trials, that evaluated the efficacy and safety of a combination of conjugated estrogens and bazedoxifene for vasomotor symptoms, quality of life, vaginal health, and bone mineral density and fracture risk reduction.
This document summarizes results from the AURA-LV clinical trial studying the efficacy and safety of voclosporin in treating lupus nephritis. The trial found that patients receiving 23.7 mg of voclosporin twice daily were over twice as likely to achieve complete renal remission at 24 weeks compared to the placebo group. They were also more likely to achieve partial remission and saw faster time to response. At 48 weeks, the low-dose voclosporin group maintained higher remission rates and saw continued improvement in proteinuria levels over time, demonstrating voclosporin's potential as a new treatment for lupus nephritis.
This clinical note discusses a patient's diabetes management. It notes low blood sugar symptoms during the night and pain/oozing from surgical wounds. It provides guidance on following the diabetes diet, exercise/medication plan, monitoring blood sugar levels, maintaining proper oral hygiene due to infection risk, and foot care. Concerns about blood sugar control and emotional state are also mentioned.
SGLT2 Inhibitors v Sitagliptin (SITA) as Add-on Therapy to Metformin Chris Sevald, PhD
SGLT2 inhibitors are the latest class of FDA-approved oral therapies to lower blood glucose in type-2 diabetes.Systematic review and meta-analysis to compare glucose-lowering and weight-loss effects of SGLT2s vs. the most-prescribed DPP-4 inhibitor, SITA. Poster presented at the 21st annual meeting of ISPOR, May, 2016, in Washington DC.
Fine Tuning Nutrient Intake Timing for Cardiac HealthInsideScientific
Cardiovascular function changes on a daily basis with potential implications for risk of heart attack and sudden cardiac death. In this webinar, Martin Young, DPhil, will discuss these cardiovascular changes and the potential mechanisms that govern these 24-hour rhythms with a particular focus on circadian clocks. These studies highlight that circadian clocks modulate processes that are critical for normal cardiovascular function, including metabolism. Daily rhythms in metabolism, in turn, influence the manner with which organs (such as the heart) respond to nutrient intake. Dr. Young illustrates the concept that the time of day at which specific macronutrients (such as lipids and proteins) are consumed dramatically impacts the heart. Dr. Young showcases the relevance of these basic science findings to human population studies.
Statins are highly effective LDL-c lowering agents that actually reduce clinical cardiovascular events. The 2013 ACC/AHA guidelines on the management of blood cholesterol recommend high-intensity statin therapy in individuals with high cardiovascular risk as assessed by the 10-year atherosclerotic cardiovascular disease risk calculator. However, a significant number of individuals do not tolerate or respond adequately to statins, and continue to have residual risk in spite of high intensity statin therapy.
There are some exciting developments in the field of lipidology. This decade has been labeled “The PCSK9 decade”. A new class of monoclonal antibodies directed against the PCSK9 glycoproteins appears very promising in further lowering LDL cholesterol and thereby cardiovascular risk. Evolocumab and alirucomab are novel PCSK9 inhibitors that can be given subcutaneously once or twice in a month, and have the potential to reduce LDL-cholesterol to very low levels without any major adverse effects.
Other classes of drugs like Apo-B antisense oligonucleotides (mipomersen), CETP inhibitors (especially anacetrapib), microsomal transfer protein inhibitors (lomitapide) also hold some promise. The future of lipid lowering therapy looks reassuring with these new developments.
Shashikiran Umakanth presented this at the Egyptian Association of Endocrinology, Diabetes & Atherosclerosis (EAEDA) 2014 conference at Alexandria, Egypt. This conference was help in association with Endocrine Society, USA and the European Association for the Study of Diabetes (EASD).
This document provides an overview of canagliflozin, an SGLT2 inhibitor used to treat type 2 diabetes. It discusses the pathogenesis of type 2 diabetes, progressive beta cell dysfunction, and the kidney's role in glucose regulation. It then reviews canagliflozin's mechanism of action as an SGLT2 inhibitor, increasing urinary glucose excretion and reducing blood glucose levels. The document summarizes canagliflozin's clinical trials, pharmacokinetics, efficacy, safety profile, and effects on renal function and lipids.
GENETIC DIET- Maria vranceanu dubai nutrition conferenceMARIA VRANCEANU
This 2-year study compared the effects of a ketogenic diet versus a nutrigenetic diet on weight loss and clinical parameters in 114 obese subjects. The nutrigenetic diet was personalized based on each subject's genetic test results. After 2 years, the nutrigenetic group had greater BMI loss (25.03% vs 17.62%), larger decreases in total cholesterol and blood glucose, and higher HDL levels compared to the ketogenic group. The study concludes that a nutrigenetically matched diet may be more effective than a standard ketogenic diet for long-term weight management and improvement of metabolic health markers.
La insulinoterapia es un arte y actualmente contamos con nuevas formulaciones y otras en proceso de investigación y aprobación. Ponencia presentada en las jornadas del benemérito H2M.
This document discusses SGLT2 inhibitors as a treatment option for type 2 diabetes mellitus. It provides background on normal glucose homeostasis and the pathophysiology of hyperglycemia in diabetes. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, causing it to be excreted in the urine. Clinical trial data shows SGLT2 inhibitors like dapagliflozin provide glycemic control as monotherapy or add-on therapy with other oral agents or insulin, with additional benefits of weight loss and blood pressure reduction. Long-term studies over 4 years show sustained glycemic control with dapagliflozin compared to other oral antidiabetic drugs.
Nueva diana hipolipemiante: terapia anti-PCSK9
02/06/2016 18:30h Casa del Corazón, Madrid
http://antipcsk9.secardiologia.es
#antiPCSK9
Resultados de la inhibición de PCSK9: superando los límites
Dr. José Luis Zamorano Gómez, Hospital Universitario Ramón y Cajal (Madrid)
@cardioXXI
Bulletproof conf 2014 dominic d agostino ketones finalDominic D'Agostino
This document summarizes a presentation by Dr. Dominic D'Agostino on metabolic therapies including ketosis and exogenous ketones. It discusses how ketones can provide resilience against conditions like hypoglycemia, seizures, and cancer. Experiments show that ketone supplementation can increase muscle power and reduce oxygen consumption during exercise at a fixed workload. Overall, the presentation explores how ketone bodies and ketosis may enhance health, performance, and protect against disease.
The document discusses recent developments in type 2 diabetes mellitus (T2DM). It covers topics like the increasing prevalence of T2DM globally, changes in pathogenesis understanding with recognition of incretin deficiency as the third defect, use of HbA1c for diagnosis, and treatment algorithms targeting both fasting and post-prandial glucose. Newer treatment options discussed include dipeptidyl peptidase-4 inhibitors, newer glucagon-like peptide-1 receptor agonists with different profiles, ultra long-acting basal insulin degludec, sodium-glucose cotransporter 2 inhibitors, glucokinase activators, and GPR40 modulators. Stem cell therapy is also mentioned as a novel approach
Dr. George L. Bakris, MD, prepared T2DM infographics for this CME activity titled "Show Me the Data: Improving Renal Outcomes With Glucose-Lowering Therapy in the Individualized Management of T2DM." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at https://bit.ly/32r5mw6. CME credit will be available until November 1, 2021.
ueda2012 glycemic control cvd debate f-d.khalifaueda2015
- While observational studies had previously suggested tighter glycemic control could reduce cardiovascular risk, these randomized trials did not find evidence of cardiovascular benefit when tightly controlling glucose levels, indicating the risks of hypoglycemia outweigh any potential benefits.
1) Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that works by inhibiting glucose reabsorption in the kidney and increasing glucose excretion in the urine.
2) Studies have shown that dapagliflozin reduces HbA1c and body weight when used as monotherapy or as add-on therapy to other glucose-lowering medications, including metformin, sulfonylureas, pioglitazone, and insulin. Reductions in HbA1c were sustained over 102 weeks.
3) Common side effects of dapagliflozin include increased urinary tract and genital infections, as well
- The document summarizes key landmark clinical trials investigating treatments for metastatic gastric cancer.
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Exenatide_CGM ADA_v6 final poster2
1. Disposition Exenatide QW + MET Placebo + MET
Randomized, n 61 56
Withdrew, n (%) 8 (13.1) 8 (14.3)
Adverse event 3 (4.9) 2 (3.6)
Lost to follow-up 2 (3.3) 3 (5.4)
Pregnancy 1 (1.6) 0 (0.0)
Protocol violation 1 (1.6) 0 (0.0)
Withdrew consent 1 (1.6) 2 (3.6)
Other 0 (0.0) 1 (1.8)
Completed, n (%) 53 (86.9) 48 (85.7)
Demographics, modified ITTa
(n=60) (n=56)
Age, y 55 ± 11 56 ± 10
Male, n (%) 33 (55.0) 32 (57.1)
Race, n (%)
White 52 (86.7) 46 (82.1)
Black or African American 3 (5.0) 5 (8.9)
Asian 3 (5.0) 4 (7.1)
Native Hawaiian or Pacific Islander 1 (1.7) 0 (0.0)
Other 1 (1.7) 1 (1.8)
Duration of diabetes, yb
9 ± 6 10 ± 8
Metformin dose, mg 1925 ± 180 1875 ± 218
Body weight, kg 90.5 ± 19.3 90.0 ± 19.1
BMI, kg/m2
32.0 ± 6.2 31.6 ± 5.4
A1C, % 8.2 ± 1.1 8.0 ± 0.9
FPG, mg/dL 178 ± 50 168 ± 54
2-h mean PPG, mg/dL 221 ± 54 221 ± 51
24-h mean glucose, mg/dL 186 ± 42 184 ± 43
Distance traveled, mg/dL 755 ± 161 730 ± 135
Total energy, (mg/(dL*h))2
12,341 ± 14,096 9953 ± 5293
Data are mean ± standard deviation, unless otherwise noted.
a
One patient in the exenatide QW group was not treated due to pregnancy and excluded from the analysis.
b
Data not available for all patients. Exenatide QW + MET, n=58; placebo + MET, n=55.
BMI, body mass index; FPG, fasting plasma glucose; ITT, intent-to-treat; PPG, postprandial glucose;
QW, once weekly.
Effects of Exenatide Once Weekly on Dynamics of 24-h Glucose Patterns in Patients With Type 2 Diabetes
Poul Strange,1
James A. Ruggles,2
Sergey Zhuplatov,2
Michael F. Miller1
1
Integrated Medical Development, Princeton Junction, NJ, USA; 2
AstraZeneca, Fort Washington, PA, USA 1048-P
Presented at the American Diabetes Association’s 76th Scientific Sessions (ADA 2016), New Orleans, LA, June 10–14, 2016.Supported by:
Conclusions
• Treatment with exenatide QW significantly reduced
glycemic fluctuations, such as distance traveled and energy,
compared with placebo
• Energy spectrum analysis showed that reductions in energy
with exenatide QW were confined to slower glucose changes
rather than fast changes
• Among patients treated with exenatide QW, the younger
patients with the highest baseline 24-h mean glucose tended
to have the highest total energy with the higher peaks at the
lower frequencies
• There were more notable differences in patients who received
placebo; energy tended to increase with decreasing age and
increasing 24-h mean glucose
• Thus, exenatide QW substantially reduced 24-h glucose
in the overall population, but effects on 24-h glucose were
manifested differently depending on age and baseline
glucose
• Exenatide QW numerically reduced total energy from baseline across
almost all baseline subgroups, with differences depending on age and
24-h mean glucose at baseline
• According to the MADz analysis, exenatide QW caused greater
reductions in 24-h mean glucose profiles in patients with higher baseline
24-h mean glucose (Figure 5); conversely, energy spectrum analysis
demonstrated modest effects on the energy spectrum in patients with
high baseline 24-h mean glucose but substantial effects on the energy
spectrum in patients with lower baseline 24-h mean glucose (Figure 6)
• Similar differential effects were observed as a function of age
• In older patients with higher baseline 24-h mean glucose, exenatide
QW reduced overall glucose equally throughout 24 h, whereas in
younger patients with lower baseline mean 24-h glucose, exenatide
QW dampened excursions in the 24-h glucose profile, resulting in a
profile that appeared similar to profiles previously observed in individuals
without diabetes
• Results were similar at Week 4 for energy spectrums analyzed by
baseline age and 24-h mean glucose
References
1. Suh S, et al. Diabetes Metab J. 2015;39(4):273–282.
2. Grimm M, et al. Postgrad Med. 2013;125(3):47–57.
3. Miller M, et al. J Diabetes Sci Technol. 2007;1(5):630–638.
Acknowledgments
The study (NCT02288273) was supported by AstraZeneca. The authors would
like to acknowledge Karen Goldsborough of AstraZeneca for her management
of study operations. Amanda Sheldon, PhD, CMPP, of inScience Communi-
cations, Springer Healthcare (Philadelphia, PA, USA), provided medical writing
support funded by AstraZeneca.
Figure 2. Comparison of Change From Baseline in Mean
24-h Glucose Profiles at Week 10, as Shown by MADz
Cl, confidence interval; MET, metformin; QW, once weekly; SE, standard error.
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Glucose(mg/dL)
Exenatide QW + MET
Placebo + MET
Exenatide QW – Placebo
Zero
Upper 95% Cl
Lower 95% Cl
± 2x SE of treatment difference
–60
30
20
10
0
–10
–20
–30
–40
–50
Time of Day (hours)
Figure 3. Exenatide QW Significantly Reduced Distance
Traveled and Total Energy of Daily Glucose Fluctuations
Compared With Placebo at Week 10
Data are LS mean change from baseline ± standard error.
Total energy = sum of squared frequency times amplitude of Fourier coefficients for the 24-h individual average glucose
curves averaged for a week over 24 h.
*P<0.01, treatment difference between LS mean changes from baseline.
LS, least-squares; MET, metformin; QW, once weekly.
–100
–40
–60
–80
40
20
–20
0
–61.5
–5.2
–70.2
*
10.8
ΔinDistanceTraveled(mg/dL)
Week 4 Week 10
–12,000
0
–4000
–8000
20,000
12,000
16,000
4000
8000
–4189
9999
–2463
*
2430
ΔinTotalEnergy(mg/(dL*h))2
Week 4 Week 10
Exenatide QW + MET (n=60) Placebo + MET (n=56)
Figure 4. At Week 10, Reductions in Energy With Exenatide QW
Affected Slower Glucose Changes Rather Than Fast Changes
880
820
760
700
640
580
520
460
400
340
280
220
160
100
40
0
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW Posterior Geometric Mean Total Energy (24 cycles) = 7171 (mg/(dL*h))2
Placebo Posterior Geometric Mean Total Energy (24 cycles) = 9947 (mg/(dL*h))2
95% Probability Bounds on the Difference (Exenatide QW – PBO): –4453 to –587 (mg/(dL*h))2
Energy Spectrum Analysis
Exenatide QW + MET
Placebo + MET
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Figure 6. Energy Spectra at Week 10 Analyzed by Baseline Age and 24-h Mean Glucose
Figure 5. MADz at Week 10 Analyzed by Baseline Age and 24-h Mean Glucose
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 133.6 mg/dL with 95% probability bounds: 113.6–153.8 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 150.8 mg/dL with 95% probability bounds: 128.5–173.2 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –17.2 mg/dL with 95% probability bounds: –47.1 to 13.2 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 154.8 mg/dL with 95% probability bounds: 139.9–169.8 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 179.9 mg/dL with 95% probability bounds: 161.6–197.9 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –25.1 mg/dL with 95% probability bounds: –48.6 to –1.6 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 173.9 mg/dL with 95% probability bounds: 156.6–192.1 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 206.2 mg/dL with 95% probability bounds: 185.3–227.1 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –32.3 mg/dL with 95% probability bounds: –59.3 to –4.5 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Baseline age = 45 y
Baseline 24-h mean glucose = 140 mg/dL
Exenatide QW + MET: Posterior mean 24-h glucose = 128 mg/dL with 95% probability bounds: 111.3–144.6 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 151 mg/dL with 95% probability bounds: 134.1–167.8 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –23 mg/dL with 95% probability bounds: –46.6 to 0.6 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 149.1 mg/dL with 95% probability bounds: 137.9–160.2 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 180.1 mg/dL with 95% probability bounds: 168.5–191.4 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –31 mg/dL with 95% probability bounds: –47.4 to –14.7 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 168.3 mg/dL with 95% probability bounds: 152.6–184.2 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 206.4 mg/dL with 95% probability bounds: 190.2–222.8 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –38.1 mg/dL with 95% probability bounds: –60.9 to –15.3 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 123.3 mg/dL with 95% probability bounds: 104.1–142.3 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 151.1 mg/dL with 95% probability bounds: 131.8–170.6 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –27.8 mg/dL with 95% probability bounds: –55.3 to –0.6 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 144.5 mg/dL with 95% probability bounds: 129.4–159.4 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 180.2 mg/dL with 95% probability bounds: 164.1–195.8 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –35.7 mg/dL with 95% probability bounds: –58.1 to –13.5 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
CGMGlucose(mg/dL)
Exenatide QW + MET Posterior Mean
Placebo + MET Posterior Mean
Exenatide QW + MET: Posterior mean 24-h glucose = 163.6 mg/dL with 95% probability bounds: 144.1–182.9 mg/dL
Placebo + MET: Posterior mean 24-h glucose = 206.5 mg/dL with 95% probability bounds: 186.4–226.4 mg/dL
Difference (Exenatide QW – Placebo): Posterior mean 24-h glucose = –42.9 mg/dL with 95% probability bounds: –71 to –15.1 mg/dL
80
270
250
230
210
190
170
150
130
110
90
Time of Day (hours)
Baseline age = 45 y
Baseline 24-h mean glucose = 182 mg/dL
Baseline age = 45 y
Baseline 24-h mean glucose = 220 mg/dL
Baseline age = 65 y
Baseline 24-h mean glucose = 140 mg/dL
Baseline age = 65 y
Baseline 24-h mean glucose = 182 mg/dL
Baseline age = 65 y
Baseline 24-h mean glucose = 220 mg/dL
Baseline age = 56 y
Baseline 24-h mean glucose = 140 mg/dL
Baseline age = 56 y
Baseline 24-h mean glucose = 182 mg/dL
Baseline age = 56 y
Baseline 24-h mean glucose = 220 mg/dL
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 7910 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 10,509 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.46 to 1.24
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0
100
200
300
400
500
600
700
800
900
1000
1150
1300
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 8850 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 12,156 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.49 to 1.07
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 9796 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 13,867 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.45 to 1.12
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 7171 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 9947 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.55 to 0.94
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 7938 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 11,348 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.48 to 1.02
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 6682 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 9631 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.44 to 1.1
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 6037 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 8442 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.5 to 1.03
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 6410 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 8599 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.5 to 1.11
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Exenatide QW + MET Posterior Geometric Mean Total Energy (24 cycles) = 5396 (mg/(dL*h))2
Placebo + MET Posterior Geometric Total Energy (24 cycles) = 7298 (mg/(dL*h))2
95% Probability Bounds on the Ratio (Exenatide QW/Placebo) 0.47 to 1.16
0 1 2 3 4 5 6 7 8 9
Number of Cycles per 24 Hours
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
EnergyComponent(mg/(dL*h))2
Exenatide QW + MET (n=51)
Placebo + MET (n=48)
60% Probability Bounds
95% Probability Bounds
99.6% Probability Bounds
Baseline age = 45 y
Baseline 24-h mean glucose = 140 mg/dL
Baseline age = 45 y
Baseline 24-h mean glucose = 182 mg/dL
Baseline age = 45 y
Baseline 24-h mean glucose = 220 mg/dL
Baseline age = 65 y
Baseline 24-h mean glucose = 140 mg/dL
Baseline age = 65 y
Baseline 24-h mean glucose = 182 mg/dL
Baseline age = 65 y
Baseline 24-h mean glucose = 220 mg/dL
Baseline age = 56 y
Baseline 24-h mean glucose = 140 mg/dL
Baseline age = 56 y
Baseline 24-h mean glucose = 182 mg/dL
Baseline age = 56 y
Baseline 24-h mean glucose = 220 mg/dL
–– Distance traveled: arc length of the mean 24-h glucose curve
• Sum of the absolute difference in glucose concentrations for 24 h
of consecutive glucose measurement
–– Total energy of daily glucose fluctuation
• Sum of squared frequency times amplitude of Fourier coefficients for the
24-h individual average glucose curves averaged for a week over 24 h
–– Energy spectrum analysis
• Individual squared frequency times amplitude Fourier terms plotted versus
frequency
–– Total energy analyzed by age (45, 56, and 65 y) with baseline 24-h mean
glucose (140, 182, and 220 mg/dL)
• This was a Bayesian linear model analysis of the total energy together with
the components of energy within the frequency domain. The linear model
included study arm as well as baseline age and 24-h mean glucose. Prior
distributions on the regression coefficients were chosen to be relatively flat
117 Adult Patients
Age 18–75 y
A1C ≥7% to ≤10%
on MET XR
Background diabetes treatment
MET XR
Randomized Treatment
10-wk intervention period
Week
Follow-up
0
CGM CGM CGM
4 10
4-wk lead-in
period
Exenatide QW 2.0 mg (n=61)
Placebo (n=56)
Methods
CGM, continuous glucose monitoring; MET XR, metformin extended release.
• Beginning at the first lead-in visit, patients with T2D were counseled on medical
nutrition and exercise
• Following lead-in, patients were randomized 1:1 to receive double-blind exenatide
QW 2.0 mg plus open-label metformin extended release (XR) 1500 or 2000 mg
once daily, or placebo microspheres plus metformin XR for 10 weeks
• Glucose concentration was measured every 5 min over 7 days during the last
week of lead-in (baseline), Week 4, and Week 10 using a Dexcom G4®
CGM
system (Dexcom, San Diego, CA, USA)
Statistical Analyses
• Efficacy and safety were assessed in the modified intent-to-treat (ITT) population,
consisting of all randomized patients who received ≥1 dose of study drug
• CGM data were analyzed for exploratory measures of glucose fluctuation
–– Comparison of the adjusted mean 24-h glucose curves using CGM profiles at
Week 10 was based on maximum amplitude of deviation from zero (MADz).
Fourier coefficients for individual patient CGM data from each period were
derived using 24 h as the longest cycle.3
The data were then aggregated
across the whole treatment group for that period resulting in a defined group
function for each period by treatment from which changes from baseline
and treatment difference functions were derived. To control for multiplicity, a
bootstrap was performed to define the 95% confidence bounds of the MADz
by time point
Figure 1. Study Design
Introduction
• Although normalization of A1C for patients with type 2 diabetes
(T2D) is an important therapeutic goal, the ability of a medication
to approximate normal daily glucose excursions is also of interest
when optimizing a patient’s glucose-lowering medications,1
as large
fluctuations confer risk of hypoglycemia
• The glucagon-like peptide-1 receptor agonist exenatide once weekly
(QW) improves glycemic control in a glucose-dependent manner
leading to robust reductions in A1C, weight loss, and a low risk of
hypoglycemia2
• This randomized controlled trial used continuous glucose monitoring
(CGM) to investigate the effects of exenatide QW compared with
placebo on 24-h glucose fluctuations in patients with T2D on
metformin therapy
• For this study, the objective was to examine the effects of exenatide
QW on exploratory outcomes related to daily glucose control by
analyzing the dynamics of 24-h glucose
Results
Table 1. Patient Disposition and Baseline Demographics and
Characteristics
The 60% credible interval of the mean difference, Exenatide QW – Placebo, excludes 0 if the study arm means fall outside of the tan region.
The 95% credible interval of the mean difference, Exenatide QW – Placebo, excludes 0 if the study arm means fall outside of the blue region.
The 95% credible interval of the maximum absolute difference, Exenatide QW – Placebo, excludes 0 if the study arm means fall outside of the dotted curves.
MET, metformin; QW, once weekly.