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
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Teneligliptin the next generation gliptinAKSHATA RAO
Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
Silvio E. Inzucchi, MD, prepared useful Practice Aids pertaining to type 2 diabetes management for this CME activity titled "The Role of SGLT2 Inhibitors in Type 2 Diabetes: CV, Metabolic, and Renal Considerations." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2l4h3Ss. CME credit will be available until June 27, 2019.
VILDAGLIPTIN: DPP-IV INHIBITOR
Generic name: Vildagliptin
Brand name: Galvus
Treatment for: type 2 diabetes
selective inhibitor of dipeptidyl-
peptidase IV (DPP-IV)
- the first in a new class of oral antidiabetic agents
- known as dipeptidyl peptidase IV inhibitors
(DPP-IV) inhibitors
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Teneligliptin the next generation gliptinAKSHATA RAO
Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
Silvio E. Inzucchi, MD, prepared useful Practice Aids pertaining to type 2 diabetes management for this CME activity titled "The Role of SGLT2 Inhibitors in Type 2 Diabetes: CV, Metabolic, and Renal Considerations." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2l4h3Ss. CME credit will be available until June 27, 2019.
VILDAGLIPTIN: DPP-IV INHIBITOR
Generic name: Vildagliptin
Brand name: Galvus
Treatment for: type 2 diabetes
selective inhibitor of dipeptidyl-
peptidase IV (DPP-IV)
- the first in a new class of oral antidiabetic agents
- known as dipeptidyl peptidase IV inhibitors
(DPP-IV) inhibitors
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
New treatment for Diabetes Mellitus and Drugs to treat HypoglycemiaFarazaJaved
This ppt covers recently FDA approved treatment of DM and other drugs that are in clinical pipelines or still under consideration. 2nd portion of ppt covers protocol used to treat hypoglycemia in different situations.
Nuevo grupo terapeútico en Diabetes Mellitus tipo 2.
Inhibidores del cotransportador sodio-glucosa.
Análisis de los estudios de desarrollo y revisión bibliográfica
Glp 1-based therapies for treatment of type 2 diabetes update on the benefit...Abdulameer Alashbal
GLP-1R agonists lower glycated haemoglobin by about 0.6–1% and induce weight loss. DPP-4 inhibitors reduce glycated haemoglobin by 0.5–0.6% and have no effect on weight. The GLP-1–related drugs arrived in clinical practice with much fanfare and anticipation. DPP- 4 enzyme is a ubiquitous cell-membrane protein, expressed in many tissues, including lymphocytes, which has raised some concerns about the long-term effects of DPP-4 inhibitors, especially on immune function. Data consistent with case reports and animal studies indicate an increased risk for pancreatitis with GLP-1-based therapy and also raise caution about the potential long-term actions of these drugs to promote pancreatic and thyroid cancers. This lecture will review the incretin-based therapies with focus on their benefits and their potential transient and serious side effects.
MFLN Nutrition and Wellness New Medications for Type 2 Diabetesmilfamln
Do your patients manage their diabetes by eating well and being active? Or do they need medication to help control their blood sugar? What medications are the most effective and what is new to the market? Tune in to this webinar to guide you through what is available and most effective to help your patients better control their type 2 diabetes.
Learning Objectives:
1. Understand the current paradigm for the treatment of type 2 diabetes.
2. Compare and contrast pros and cons of newer medications for the Treatment of type 2 diabetes.
3. Modify a treatment plan correctly and efficiently based on the side effect profiles of newer medications for the treatment of type 2 diabetes.
Our aim is to reduce morbidity and mortality related to Non communicable diseases such as hypertension, diabetes, cardiovascular disease, stroke, Obesity, Cancer and lifestyle diseases among those least able to withstand the burden of the disease.
Infertility is defined as the inability of a couple to conceive after at least one year of regular unprotected intercourse.
Male infertility refers to a male's inability to cause pregnancy in a fertile female.
IDD situation in our country has improved
A good number of thyroid disorder patients are either undiagnosed and or untreated
Thyroid disorder in pregnancy- Rate high
As a sound thyroid functioning status is crucial for growth, development in children; reproduction, psychological and general wellbeing in adults, we must be proactive in screening, diagnosing and treating our patients.
Over the past several years it has been proved that maternal thyroid disorder influence the outcome of mother and fetus, during and also after pregnancy. The most frequent thyroid disorder in pregnancy is maternal hypothyroidism. It is associated with fetal loss, placental abruptions, pre-eclampsia, preterm delivery and reduced intellectual function in the offspring.1 In pregnancy, overt hypothyroidism is seen in 0.2% cases2 and sub clinical hypothyroidism in 2.3% cases3. Fetal loss, fetal growth restriction, pre-eclampsia and preterm delivery are the usual complications of overt hyperthyroidism (low TSH and high T3, T4) seen in 2 of 1000 pregnancies whereas mild or sub clinical hyperthyroidism (suppressed TSH alone) is seen in
1.7% of pregnancies and not associated with adverse outcomes4. Autoimmune positive euthyroid pregnancy shows doubling of incidence of miscarriage and preterm delivery. Worldwide more than 20 million people develop neurological sequel due to intra uterine, iodine deprivation5. Other problems of thyroid disorders in pregnancy are post partum thyroiditis, thyroid nodules and cancer, hyper emesis gravidarum etc. Debates and disputes persist regarding several protocol and management plan in this specific spectrum of diseases.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
Dapagliflozin- a novel SGLT2 inhibitor
1. Dr Shahjada Selim
Assistant Professor
Department of Endocrinology
Bangbandhu Sheikh Mujib medical University, Dhaka
Dapagliflozin:
A novel insulin-independent
approach to remove excess glucose
5. Normal renal glucose handling1–3
SGLT, sodium-glucose co-transporter.
1. Wright EM. Am J Physiol Renal Physiol 2001;280:F10–18; 2. Lee YJ, et al. Kidney Int Suppl 2007;106:S27–35;
3. Hummel CS, et al. Am J Physiol Cell Physiol 2011;300:C14–21.
SGLT2
Glucose
Majority of glucose is
reabsorbed by SGLT2
(90%)
Proximal tubule
Remaining glucose is
reabsorbed by SGLT1
(10%)
Minimal to no
glucose excretion
Glucose
filtration
6. Dapagliflozin
Proximal tubule
Glucose
filtration
1. FORXIGA Summary of Product Characteristics
Dapagliflozin selectively inhibits SGLT2 in the renal proximal tubule1
SGLT2
Glucose
Dapagliflozin
SGLT2
Dapagliflozin
Increased
urinary glucose
excretion
7. The benefits of dapagliflozin’s novel
mechanism of action
Dapagliflozin offers an insulin-
independent mechanism that can be
used as add-on therapy1,4
1. Bailey CJ, et al. Lancet 2010;375:2223–33;
2. FORXIGA Summary of Product Characteristics
8. The benefits of dapagliflozin’s novel
mechanism of action
Dapagliflozin inhibition of SGLT2 results in
daily urinary glucose excretion of
approximately 70g,2 providing:
Significant and sustained HbA1c reductions
versus placebo when added to metformin1,3
Secondary benefit of weight loss1
1.Bailey CJ, et al. Lancet 2010;375:2223–33;
2. FORXIGA Summary of Product Characteristics
3.Bailey CJ, et al. Poster 988-P. Poster presented at 71st Scientific Sessions of the American Diabetes Association,
San Diego, California, 24–28 June, 2011
9. Side Effects
Increased susceptibility
to infection
Polyuria
Hypotension
Hyperkalemia
Impaired renal function
Increase in LDL
10. Urinary tract infection risks
likely to increase as…
Increased glucose in urine
Genital mycotic > urinary tract infections
(UTIs)
At increased risk:
Females
11-15% F > 1-8% M
Dose-independent
Vasilakou D, Karaglannis T, Athanasiadou E, et al. Ann Intern Med. 2013;159:262-74.
11. Infections
Drug Dose
Urinary tract
infections
Genital mycotic infections
Female Male
Canagliflozin
100mg 5.9% 10.4% 4.2%
300mg 4.3% 11.4% 3.7%
Dapagliflozin
5mg 5.7% 8.4% 2.8%
10mg 4.3% 6.9% 2.7%
Empagliflozin
10mg 9.3% 5.4% 3.1%
25mg 7.6% 6.4% 1.6%
1. Invokana® (capagliflozin) packageinsert. Titusville (NJ): Janssen Pharmaceuticals; May 2014. 2. Farxiga® (dapagliflozin) package insert. Prineton (NJ): Bristol-Myers Squibb; Aug 2014.
3. Jardiance® (empagliflozin) package insert. Ridgefield (CT): Boehringer Ingelheim; Aug 2014. 4. Yang XP, Lai D, Zhong XY, et al. Eur J Clin Pharmacol. 2014; 70:1149-58.
5. Zang M, Zhang L, Wu B, et al. Diabetes Metab Res Rev. 2014;30:204-21. 6. Liakos A, Karagiannis T, Athanasiadou E, et al. Diabetes Obes Metab. 2014; 16: 984-93.
12.
13. Kidney Function
Osmotic diuresis & volume depletion
Polyuria (including nocturia) resulting in dehydration,
hypovolemia, syncope, etc.
Increased risk if > 75yo, eGFR < 60ml/min or on loop
diuretics
Dose-dependent decrease in blood pressure
Systolic BP 3-6mmHg
Diastolic BP 1-2mmHg
1. Vasilakou D, Karaglannis T, Athanasiadou E, et al. Ann Intern Med. 2013;159:262-74.
2. Fujita Y, Inagaki Y. J Diabetes Invest. 2014;5:265-75.
14. Dapagliflozin: Reductions in HbA1c were sustained over 102 weeks
Data are mean change from baseline after adjustment for baseline value. Data after rescue are excluded.Analyses were obtained by
longitudinal repeated measures analyses. CI, confidence interval.
Adapted from Bailey CJ et al. Poster #988-P. Poster presented at 71st Scientific Sessions of the American Diabetes Association, San Diego, California, June
24–28, 2011.
Study week
–1.2
–0.8
–0.6
–0.4
0.2
0 16 37 50 63 76 10289
0.0
HbA1c(%)
meanchangefrombaseline
8 24
Primary endpoint
–1.0
–0.2
–5
0
–10
Dapagliflozin 10 mg +
metformin
(Mean baseline HbA1c 7.92% [63
mmol/mol])
Placebo + metformin
(Mean baseline HbA1c 8.11% [65
mmol/mol])
(n=133)
(n=132)
HbA1c(mmol/mol)
meanchangefrombaseline
+0.02%
(0.2
mmol/mol)
(95% Cl,
–0.20 to 0.23%;
n=28)
–0.78%
(–8.5 mmol/mol)
(95% Cl,
–0.97 to –0.60%;
n=57)
0.80%
(8.8 mmol/mol)
difference
15. 1. Ferrannini E et al. Diabetes Care 2010;33:2217–2224. 2. Bailey CJ et al. Lancet 2010;375:2223–2233.
3. Strojek K et al. Diabetes Obes Metab 2011;13:928–938. 4. Wilding JPH et al. Ann Intern Med 2012;156:405–415.
Dapagliflozin: Consistent reduction in HbA1c at Week 24 across studies
Baseline HbA1c:
7.91%; 63 mmol/mol
MeanchangeinHbA1c(%)
–0.23
(-3 mmol/mol)
–0.89*
(-10 mmol/mol)
–0.84*
(-9 mmol/mol)
–0.30
(-3 mmol/mol)
–0.82*
(-9 mmol/mol)
–0.13
(-1 mmol/mol)
–0.96*
(-10 mmol/mol)
–0.39
(-4 mmol/mol)
Baseline HbA1c:
8.05%; 64 mmol/mol
Baseline HbA1c:
8.11%;
65 mmol/mol
Baseline HbA1c:
8.53%; 70 mmol/mol
Add-on to a
SU3
Add-on to metformin2Monotherapy1 Add-on to insulin4
These data are taken from different studies and the results should not be compared across studies.
*Statistically significant vs. placebo using Dunnett’s correction.SU, sulphonylurea.
Dapagliflozin (10 mg)
Placebo
p<0.0001 p<0.0001 p<0.0001 p<0.001
16. Dapagliflozin: secondary benefit of weight loss over 102
weeks
Weight loss at 24 weeks, with decreased waist circumference is consistent with a reduction of body-fat mass 1
In a separate study, weight loss was mainly attributable to reduction in body fat mass rather than loss of fluid or lean
tissue3 #
Adjustedmeanchange
frombaselinebodyweight(kg)
24 weeks (LOCF analysis)1
–1.70 kg
(n=95)
95% Cl
(-2.48 to -0.91)
–2.9 kg
(n=133)
95% CI
(-3.3 to -2.4)
–0.9 kg
(n=136) 95%CI
-1.4 to -0.4
2.0 kg
difference
p<0.0001
+1.36 kg
(n=73)
95% Cl
(0.53 to 2.20)
3.1 kg
difference
p value not
calculated
Data are mean change from baseline after adjustment for baseline value (mean baseline weight: dapagliflozin 86.3 kg, placebo 87.7 kg).
24-week data are based on LOCF analysis excluding data after rescue; 102-week data are based on longitudinal repeated measures analysis and include data
after rescue.
# As measured by dual energy absorptiometry at 24 weeks
1. Bailey CJ, et al. Lancet 2010;375:2223–33; 2. Bailey CJ, et al. Poster 988-P. Poster presented at 71st Scientific Sessions of the American Diabetes
Association, San Diego, California, June 24–28, 2011; 3. Bolinder J, et al. J Clin Endocrinol Metab 2012;97:1020–31.
102 weeks (repeated measures analysis)2
Dapagliflozin 10 mg
+ metformin
Dapagliflozin 10 mg
+ metformin
Placebo
+ metformin
Placebo
+ metformin
Adapted from Bailey CJ, et al. (2010) & Bailey CJ, et al. (2011)
17. Reductions in HbA1c with insulin + dapagliflozin
compared with insulin + placebo at 24 weeks
1. Wilding J, et al. Ann Intern Med 2012;156:405–415.
2. FORXIGA™. Summary of product characteristics.
Adapted from Wilding J, et al. 2012
Last observation carried forward (LOCF). Data are adjusted mean change from baseline. Mean HbA1c at baseline were 8.47% (69
mmol/mol) for insulin + placebo and 8.57% (70 mmol/mol) for insulin + dapagliflozin 10mg.
Consider a reduction in insulin dose on commencement of dapagliflozin to reduce the risk of hypoglycaemia2
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
Adjustedmeanchangefrom
baselineHbA1c(%)
Adjustedmeanchangefrom
baselineHbA1c(mmol/mol)
Dapagliflozin 10 mg +
insulin
Placebo +
insulin
–0.96%
(–10.5 mmol/mol)
(n=194)
–0.39%
(–4.3 mmol/mol)
(n=193)
0.57% (6.2 mmol/mol)
difference
(95% CI, –0.72 to –0.42%)
p<0.001
-10
-5
0
18. Uptitration of insulin dosing is less pronounced in patients treated
with insulin + dapagliflozin compared with insulin + placebo ± OADs
1. Wilding JPH et al. Ann Intern Med 2012;156:405–415.
2. FORXIGA™. Summary of product characteristics..
Dapagliflozin
190
Change in total daily insulin dose (units)
from baseline1:
At 24 weeks
placebo + insulin – 8% increase
dapagliflozin + insulin – 1.5% decrease
At 48 weeks
placebo + insulin – 14% increase
dapagliflozin + insulin – 1% decrease
Patients needing rescue therapy or
withdrawn from study for not achieving
glycaemic targets:1
Placebo + insulin – 42.8%
dapagliflozin 10mg + insulin – 15.3%
Baseline mean daily insulin dose (units):
• Insulin + placebo = 73.7
• Insulin + dapagliflozin 10mg = 78.0
• Consider a reduction in insulin dose on
commencement of dapagliflozin to
reduce the risk of hypoglycaemia2
20. Weight Loss
Group Low Dose (kg) High Dose (kg)
Canagliflozin 2.2 3.3
Canagliflozin +
Insulin
1.9 2.4
Dapagliflozin 2.2 2
Dapagliflozin +
insulin
1 1.7
Empagliflozin 2.5 2.8
Empagliflozin +
insulin
3 3
1. Invokana® (capagliflozin) packageinsert. Titusville (NJ): Janssen Pharmaceuticals; May 2014. 2. Farxiga® (dapagliflozin) package insert. Prineton (NJ): Bristol-Myers Squibb; Aug 2014.
3. Jardiance® (empagliflozin) package insert. Ridgefield (CT): Boehringer Ingelheim; Aug 2014. 4. Yang XP, Lai D, Zhong XY, et al. Eur J Clin Pharmacol. 2014; 70:1149-58.
5. Zang M, Zhang L, Wu B, et al. Diabetes Metab Res Rev. 2014;30:204-21. 6. Liakos A, Karagiannis T, Athanasiadou E, et al. Diabetes Obes Metab. 2014; 16: 984-93.
21. Hypoglycemia
Insulin-independent mechanism of action
Low risk when used as monotherapy
Comparable to that of metformin or sitagliptin
Increased risk with insulin and insulin secretagogues
SGLT2is lower the renal reabsorption of glucose
threshold without completely inhibiting it
Renal threshold of < 70mg/dL
1. Chen LH, Leung PS. Diabetes Obes Metab. 2013;15:392-402.
2. Jung CH, Jang JE, Park JY. Diabetes Metab J 2014;38261-73.
3.. Fujita Y, Inagaki Y. J Diabetes Invest. 2014;5:265-75.
22. Dapagliflozin: Hypoglycemia
Group
Hypoglycemic Events
Minor Major
5mg 10mg 5mg 10mg
Monotherapy 0% 0% 0% 0%
Add-on
metformin
1.5% 0.7% 0% 0%
Add-on
glimepiride
5.5% 6.0% 0% 0%
Add-on
pioglitazone
2.1% 0% 0% 0%
Add-on
insulin
43.4% 40.3% 0.5% 0.5%
1. Farxiga® (dapagliflozin) package insert. Prineton (NJ): Bristol-Myers Squibb; Aug 2014. 2. Zang M, Zhang L, Wu B, et al. Diabetes Metab Res Rev. 2014;30:204-21.
27. 1.1 Dapagliflozin in a dual therapy regimen in
combination with metformin is recommended as
an option for treating type 2 diabetes, only if it is
used as described for dipeptidyl peptidase-4
(DPP-4) inhibitors inType 2 diabetes: the
management of type 2 diabetes (NICE clinical
guideline 87).
NICE TA288
http://publications.nice.org.uk/dapagliflozin-in-combination-
therapy-for-treating-type-2-diabetes-ta288
28. 1.2 Dapagliflozin in combination with insulin with or without
other antidiabetic drugs is recommended as an option for
treating type 2 diabetes.
1.3 Dapagliflozin in a triple therapy regimen in combination with
metformin and a sulfonylurea is not recommended for treating
type 2 diabetes, except as part of a clinical trial.
NICE TA288
http://publications.nice.org.uk/dapagliflozin-in-combination-
therapy-for-treating-type-2-diabetes-ta288
The three c-glucosidase SGLT2 inhibitors available are cana-, dapa- and empa-gliflozin. There are several others being researched and undergoing trials.
The first to be approved was canagliflozin in January of 2013. It was approved in two dosage strengths, 100 and 300mg. However, 100mg is the maximum dose for CrCl < 45-60ml/min and use is not recommended in CrCl < 30-45ml/min
- Increase in non-fatal stroke?
Dapagliflozin was the second to be FDA approved in January of 2014 also in two dosage strengths with recommendations to avoid use in CrCl < 60 ml/min. However, dapagliflozin was actually the first SGLT2 to complete phase III trials and the first to be presented to the FDA for approval. However, the FDA denied its first application stating the increased incidence of bladder and breast cancer seen in clinical trials warranted further study before approval. Thus after several additional long term studies it was approved a year after canagliflozin. The increased incidence of bladder cancer was 10 cases out of 6045 or 0.17% compared to 1 out of 3512 or 0.1% in placebo/active comparators and the increased incidence of breast cancer was 12 cases in 2693 or 0.45% compared to 3 out of 1439 or 0.45% in placebo/active comparators. The exact relationship between dapagliflozin and these cancers is uncertain as majority of the studies were less than 90 week durations and these cancers typically take years to develop.
Empagliflozin was recently approved by the FDA in August of 2014. Again it was approved at two dosage strengths and is not recommended in CrCl < 45ml/min. Empagliflozin was developed as it is the most selective for the SGLT2 receptor out of the available drugs. Thus it was believed to have the potential to be safer and/or more effective.
7
8
By understanding this mechanism of action and the other consequences of inhibiting glucose reabsorption, such as reduction of sodium and water reabsorption as well as potential reduced excretion of potassium, one begin to hypothesize the potential side effects of this class of medications.
Avoid use in CrCl <45-60ml/min
Dose-dependent decrease in eGFR (~2-6ml/min)
Pre-renal, not direct renal injury
Volume depletion 1-3%
3-8% if >75yo, eGFR<60, or on loop diuretics
Glycemic efficacy declines with decreased renal function
However, improves overtime (~1-3ml/min)
Helps prevent and improve albuminuria
14
16
So then dapagliflozin, again you see a slight decrease with combination therapy in comparison to monotherapy but not as significant as with canagliflozin. You also see some added benefit with the increased dose from 5mg to 10mg, however again not as significant as with canagliflozin. Presumably due to this lack of significant difference and improved glycemic control with the higher dose of 10mg, many studies did not even include the 5mg dose. Dapagliflozin was studied as third add on treatment with either metformin and sitagliptin or insulin and an oral antidiabetic agent (most often metformin).
Add on glimepiride: in comparison to placebo (glimepiride alone) with 2.1% minor and 0% major
Add on insulin: in comparison to placebo (insulin +/- OADs alone) with 34% minor and 0.5% major