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
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
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
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
GLP-1 is an incretin (hormone that increases insulin secretion in response to a meal), which is a 30-amino acid peptide secreted in response to the oral ingestion of nutrients by intestinal L cells.
GLP-1 receptors (GLP-1R) are located in islet cells, central nervous system, and other organs. GLP-1 is metabolized by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin effect is a phenomenon whereby a glucose load delivered orally produces a much greater insulin secretion than the same glucose load administered intravenously.
This presentation is an overview of the entire GLP-1 system, followed by an introduction to leveraging its therapeutic potential using GLP-1 analogues (Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin).
Shashikiran Umakanth delivered this talk at Manipal on 30th November, 2015
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.
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
GLP-1 is an incretin (hormone that increases insulin secretion in response to a meal), which is a 30-amino acid peptide secreted in response to the oral ingestion of nutrients by intestinal L cells.
GLP-1 receptors (GLP-1R) are located in islet cells, central nervous system, and other organs. GLP-1 is metabolized by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin effect is a phenomenon whereby a glucose load delivered orally produces a much greater insulin secretion than the same glucose load administered intravenously.
This presentation is an overview of the entire GLP-1 system, followed by an introduction to leveraging its therapeutic potential using GLP-1 analogues (Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin).
Shashikiran Umakanth delivered this talk at Manipal on 30th November, 2015
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.
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
Glucagon like peptide-1 (GLP-1) is an incretin secretory molecule. GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes (T2DM) due to their attributes such as body weight loss, protection of islet β cells, promotion of islet β cell proliferation and minimal side effects. Studies have found that GLP-1R is widely distributed on pancreatic and other tissues and has multiple biological effects, such as reducing neuroinflammation, promoting nerve growth, improving heart function, suppressing appetite, delaying gastric emptying, regulating blood lipid metabolism and reducing fat deposition. Moreover, GLP-1RAs have neuroprotective, anti-infectious, cardiovascular protective, and metabolic regulatory effects, exhibiting good application prospects. Growing attention has been paid to the relationship between GLP-1RAs and tumorigenesis, development and prognosis in patient with T2DM. Here, we reviewed the therapeutic effects and possible mechanisms of action of GLP-1RAs in the nervous, cardiovascular, and endocrine systems and their correlation with metabolism, tumours and other diseases.
efficacy and safety of Sulfad tablets in the management of NASH
patients: A randomized ,prospective, open label, multi-center,
controlled, phase III clinical trial.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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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.
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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
5. Metabolic health: a priority for the post-pandemic era
•The Lancet Diabetes & EndocrinologyPublished:March 04,
2021DOI:https://doi.org/10.1016/S2213-8587(21)00058-9
Avoiding the Coming Tsunami of Common, Chronic Disease: What the Lessons of the
COVID-19 Pandemic Can Teach Us Robert M. Califf Originally published6 Apr
2021https://doi.org/10.1161/CIRCULATIONAHA.121.053461Circulation.
26. Julio Rosenstock1, Carol Wysham2, Juan P. Frias3,
Shizuka Kaneko4, Clare J. Lee5, Laura Fernández Landó5,
Huzhang Mao5, Xuewei Cui5, Vivian T. Thieu5
Efficacy and Safety of Once Weekly
Tirzepatide, a dual GIP/GLP-1 Receptor
Agonist Versus Placebo as Monotherapy
in People with Type 2 Diabetes
(SURPASS-1)
1Dallas Diabetes Research Center at Medical City, Dallas, TX, USA; 2Rockwood Clinic,
Spokane, WA, USA; 3National Research Institute, Los Angeles, CA, USA; 4Takatsuki Red
Cross Hospital, Osaka, Japan; 5Eli Lilly and Company, Indianapolis, IN, USA
SURPASS-1
27. SURPASS 1
Key Inclusion Criteria
• T2D
• HbA1c ≥7.0% to ≤9.5%
• BMI ≥23 kg/m2 Stable Weight
• Naïve to T2D injectable
therapya
• Have not used any oral
antihyperglycaemic
medication in the 3 months
prior to screening
Study Period I Study Period II Study Period III
Tirzepatide 5 mg QW
Tirzepatide 10 mg QW
Tirzepatide 15 mg QW
Injectable Placebo QW
2.5 mg
2.5 mg 5 mg 7.5 mg 10 mg
2.5 mg 5 mg 7.5 mg 10 mg 12.5 mg 15 mg
5 mg
Safety
Follow-up
40 weeks 4 weeks
1
weeks
2
weeks
Screening
Lead-in
-3 -2 -0 4 8 12 16 20 24 40 44
Randomisation
1:1:1:1
(N=478)
Primary
Endpoint
aExcept for the use of insulin for treatment of gestational diabetes, or short-term use (≤14 days) for acute conditions such as acute illness, hospitalisation, or elective surgery
Randomised, Double-Blind, Placebo-Controlled, Parallel Group Trial
28. HbA1c
Change from Baseline at 40 Weeks
Data are LSM (SE). Efficacy Estimand: Estimated treatment differences are LSM (95% CI). MMRM analysis, mITT population (efficacy analysis set). Treatment-regimen estimand:
ANCOVA analysis, mITT population (full analysis set).
SURPASS-1
29. Body Weight
Change from Baseline at 40 Weeks
Data are LSM (SE). Efficacy Estimand: Estimated treatment differences are LSM (95% CI). MMRM analysis, mITT population (efficacy analysis set). Treatment-
regimen estimand: ANCOVA analysis, mITT population (full analysis set).
SURPASS-1
30. Patient-Reported Outcomes in Patients
with Type 2 Diabetes Treated with
Tirzepatide or Placebo (SURPASS-1)
Kristina Boye, Maria Yu, Clare J. Lee, Huzhang Mao,
Xuewei Cui, Laura Fernández Landó, Vivian Thieu
Eli Lilly and Company, Indianapolis, USA
European Association for the Study of Diabetes, 57th Annual Meeting; Virtual; 27 September – 1 October, 2021
31. EQ-5D-5L INDEX
EQ-5D-5L Index (UK) Score (Scale <0 to 1)
– Measures overall health status
– Includes 5 dimensions: mobility; self-care; usual activities; pain/discomfort;
anxiety/depression
– Algorithm based on van Hout B et al. (2012)3
Change at 40 weeks
EQ visual analogue scale (EQ VAS) (Scale 0 – 100)
– Measures records the patient’s health-
related quality of life on a vertical visual analogue
scale
EQ VAS
32. IW-SP
IW-SP Questionnaire (Score 0 - 100)
– Measures patients’ self-perception relating to their body weight
– Includes 3 items: feel unhappy with appearance due to weight; feel
self-conscious in public due to weight; feel unhappy due to comparing
weight with others
Change at 40 weeks
APPADL Questionnaire (Score 0 - 100)
– Measures self-reported ability to perform tasks of daily living
– Includes difficulty in 7 items: getting up from floor/ground; getting
down to floor/ground; standing; climbing stairs; household
chores/yard work; moderate physical activity; strenuous physical
activity
APPADL
33. Efficacy and Safety of
Tirzepatide Versus
Semaglutide Once
Weekly as Add-on
Therapy to Metformin in
People with Type 2
Diabetes (SURPASS-2)
Melanie Davies, MD1, Juan P. Frias, MD2, Julio Rosenstock, MD3, Federico Pérez
Manghi, MD4, Laura Fernández Landó, MD5, Brandon K Bergman, PharmD5, Bing Liu,
PhD, MS5, Xuewei Cui, PhD5, Katelyn Brown, PharmD5
1Diabetes Research Centre, Leicester Diabetes Centre – Bloom, University of Leicester,
Leicester, UK; 2National Research Institute, Los Angeles, CA, USA; 3Dallas Diabetes Research
Center at Medical City, Dallas, TX, USA; 4CINME S.A., Buenos Aires, Argentina; 5Eli Lilly and
Company, Indianapolis, IN, USA
SURPASS-2
34. Study Design
Randomised, open-label, active-controlled, parallel group, multicentre, multinational trial
Key Inclusion Criteria
Type 2 diabetes
HbA1c ≥7.0% to ≤10.5% at
screening
BMI ≥25 kg/m2 with stable
weight
On stable dose of metformin
≥1500 mg/day
Key Exclusion Criteria
Type 1 diabetes
History of acute pancreatitis
eGFR <45 mL/min/1.73 m2
Use of any antihyperglycemic
treatment other than metformin
in the 3 months prior to
screening
Participating Countries: US, Argentina, Australia, Brazil, Canada, Israel, Mexico and UK. aStable doses of metformin ≥1500 mg/day for at least 3 months prior to Visit 1 and during
the screening/lead-in period. bAll tirzepatide doses were double-blinded.
SURPASS-2
41. Efficacy and Safety of
Tirzepatide, a Dual GIP/GLP-1
Receptor Agonist, Compared to
Insulin Degludec in Patients with
Type 2 Diabetes (SURPASS-3)
Bernhard Ludvik1, Francesco Giorgino2, Esteban Jódar3,
Juan P. Frias4, Laura Fernández Landó5, Katelyn
Brown5, Ross Bray5, Ángel Rodríguez5
11st Medical Department and Karl Landsteiner Institute for Obesity and
Metabolic Disorders, Landstrasse Clinic, Vienna Health Association,
Vienna, Austria, 2University of Bari Aldo Moro, Bari, Italy, 3Hospital
Universitario Quirónsalud Madrid, Madrid, Spain, 4National Research
Institute, Los Angeles, CA, USA, 5Eli Lilly and Company, Indianapolis, IN,
USA
SURPASS-3
42. Study Design
Key Inclusion Criteria
■ Type 2 diabetes
■ HbA1c ≥7.0% ≤10.5%)
■ BMI ≥25 kg/m2 with stable
weight
■ Naive to insulin therapy
(except short-term use or
treatment of gestational diabetes)
■ On stable dose of metformin,
with or without SGLT-2i
Key Exclusion Criteria
■ Type 1 diabetes
■ History of pancreatitis
■ eGFR <45 mL/min/1.73 m2
Participating Countries: Argentina, Austria, Greece, Hungary, Italy, Poland, Puerto Rico, Romania, South Korea, Spain, Taiwan, Ukraine, and the USA.
aStable doses of metformin (≥1500 mg/day) ± SGLT-2i for ≥3 months prior to Visit 1 and during the screening/lead-in period.
bThe starting dose of insulin degludec was 10 U/day ideally at bedtime, titrated to a FBG <5.0 mmol/L (<90 mg/dL), following a treat-to-target algorithm.
Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; FBG = fasting blood glucose; HbA1c = haemoglobin A1c; QD = once daily; QW = once weekly; SGLT-2i = sodium-
glucose cotransporter-2 inhibitor.
Randomisation
SURPASS-3
43. Data on left panel are LSM (SE); MMRM analysis. Data on right panel are estimated mean; Logistic regression. mITT (efficacy analysis set). Arrows on X-axis in overtime plot indicate when the maintenance dose of tirzepatide 5 mg, 10 mg, and 15 mg was
initiated. Mean insulin degludec dose at Week 52 was 48.8 U/day. Estimated treatment difference (95% CI) of tirzepatide vs. insulin degludec was: i) 5 mg, -6.4* (-7.9, -4.9) mmol/mol (-0.59%* [-0.73, -0.45]); ii) 10 mg, -9.4* (-10.9, -7.9) mmol/mol (-0.86%* [-1.00,
-0.72]); and iii) 15 mg, -11.3* (-12.8, -9.8) mmol/mol (-1.04%* [-1.17, -0.90]). *p<0.001 vs. insulin degludec.
Abbreviations: CFB = change from baseline; CI = confidence interval; HbA1c = haemoglobin A1c; LSM = least-squares mean; mITT = modified Intent-to-Treat; MMRM = mixed model repeated measures; SE = standard error.
HbA1c
Overall mean baseline HbA1c = 8.18%
(-1.93%)
(-2.20%)
- (-2.37%)
(-1.34%)
Tirzepatide 5 mg Tirzepatide 15 mg
Tirzepatide 10 mg Insulin Degludec
% of Participants Achieving
HbA1c Goals at Week 52
HbA1c over Time and Change from Baseline at Week 52
CFB
T
Z
P
5
m
g
T
Z
P
1
0
m
g
T
Z
P
1
5
m
g
I
D
e
g
T
Z
P
5
m
g
T
Z
P
1
0
m
g
T
Z
P
1
5
m
g
I
D
e
g
T
Z
P
5
m
g
T
Z
P
1
0
m
g
T
Z
P
1
5
m
g
I
D
e
g
0
20
40
60
80
100
Proportion
of
Participants
(%)
*
93
61
*
90
*
82
*
71
*
80
*
85
44
*
26
*
39
*
48
5
HbA1c <53 mmol/mol
(<7.0%)
48 mmol/mol
(6.5%)
<39 mmol/mol
(<5.7%)
SURPASS-3
44. Body Weight
Overall mean baseline weight = 94.5 kg (BMI = 33.5 kg/m2)
-7.5
-10.7
-12.9
2.3
Data on left panel are LSM (SE); MMRM analysis. Data on right panel are estimated mean; Logistic regression. mITT (efficacy analysis set). Arrows on X-axis in overtime plot indicate when the maintenance dose of tirzepatide 5 mg, 10 mg, and 15 mg was initiated. Estimated treatment difference
(95% CI) of tirzepatide vs. insulin degludec was: i) 5 mg, -9.8 kg* (-10.8, -8.8); ii) 10 mg, -13.0 kg* (-14.0, -11.9); and iii) 15 mg, -15.2 kg* (-16.2, -14.2). *p<0.001 vs. insulin degludec.
Abbreviations: BMI = body mass index; CFB = change from baseline; CI = confidence interval; LSM = least-squares mean; mITT = modified Intent-to-Treat; MMRM = mixed model repeated measures; SE = standard error.
Tirzepatide 5 mg Tirzepatide 15 mg
Tirzepatide 10 mg Insulin Degludec
Proportion of Participants with Body
Weight Loss Goals at Week 52
Body Weight over Time and Change from Baseline at Week 52
CFB
T
Z
P
5
m
g
T
Z
P
1
0
m
g
T
Z
P
1
5
m
g
I
D
e
g
T
Z
P
5
m
g
T
Z
P
1
0
m
g
T
Z
P
1
5
m
g
I
D
e
g
T
Z
P
5
m
g
T
Z
P
1
0
m
g
T
Z
P
1
5
m
g
I
D
e
g
0
20
40
60
80
100
Proportion
of
Participants
(%)
*
88
6
*
84
*
66
*
37
*
56
*
69
3
*
13
*
28
*
43
0
5% weight loss 10% weight loss 15% weight loss
SURPASS-3
45. Effect of Tirzepatide Versus Insulin
Degludec on Glycemic Control Captured
With Continuous Glucose Monitoring in
Patients With Type 2 Diabetes
(SURPASS-3 CGM)
Tadej Battelino1, Richard Bergenstal2, Angel Rodríguez3, Laura Fernández Landó3, Ross
Bray3, Zhentao Tong3, Katelyn Brown3
1Faculty of Medicine, University of Ljubljana, and University Medical Center Ljubljana, Ljubljana,
Slovenia , 2International Diabetes Center HealthPartners Institute, Minneapolis, MN, USA, 3Eli Lilly and
Company, Indianapolis, IN, USA
European Association for the Study of Diabetes, 57th Annual Meeting; Virtual; 27 September – 1 October, 2021
46. Time Spent in Target Ranges 71-180 mg/dL
at Baseline and 52 Weeks
* p<0.05, ** p<0.01, *** p<0.001 versus insulin degludec. 3.9-10 mmol/L = 71-180 mg/dL. TZP = tirzepatide.
TZP 5mg TZP 10mg TZP 15mg Insulin degludec
48% 52%
0.3%
Baseline
39% 61%
0.3% 0.3%
50% 50%
85%*
0.6%***
15%
Week
52
91%***
8%***
1%**
91%***
0.8%***
9%***
54%
0.3%
46%
75%
2%
23%
Hypoglycaemic < 3.9 mmol/L Time In Range 3.9-10 mmol/L Hyperglycaemic > 10 mmol/L
47. Average CGM Values Over 24 Hours at Baseline,
24 Weeks, and 52 Weeks
Values are in mg/dL. avg = average. cv = coefficient of variation. stdev = standard deviation. TZP = tirzepatide.
48. Effect of Tirzepatide Versus Insulin Degludec
on Liver Fat Content and Abdominal Adipose
Tissue in Patients With Type 2 Diabetes
(SURPASS-3 MRI)
Amalia Gastaldelli1, Kenneth Cusi2, Laura Fernández Landó3, Ross Bray3, Bram Brouwers3, Ángel Rodríguez3
1Institute of Clinical Physiology, CNR, Pisa, Italy, 2Division of Endocrinology, Diabetes and Metabolism,
The University of Florida, Gainesville, FL, USA, 3Eli Lilly and Company, Indianapolis, IN, USA
European Association for the Study of Diabetes, 57th Annual Meeting; Virtual; 27 September – 1 October, 2021
49. Liver Fat Content
Data are LSM (SE); ANCOVA analysis. mITT (MRI analysis set). Estimated treatment differences (ETD) are LSM (95% confidence interval) vs. insulin degludec. † p<0.05; ††† p<0.001 vs. baseline
within treatment group. ∝ represents the mean value at baseline for the respective group. Mean insulin degludec dose at Week 52 was 58.8 U/day (0.6 U/kg/day).
Abbreviations: ANCOVA = analysis of covariance; LFC = liver fat content; LSM = least-squares mean; mITT = modified Intent-to-Treat; MRI = magnetic resonance imaging; SE = standard error; TZP =
tirzepatide.
Comparison Between Individual Doses of Tirzepatide
and Insulin Degludec at Week 52
Comparison Between Pooled Data From Tirzepatide 10/15 mg
and Insulin Degludec at Week 52
-10
-8
-6
-4
-2
0
LFC
absolute
change
from
baseline
(%)
Insulin
Degludec
TZP pooled
10/15 mg
-8.09†††
-3.38†††
ETD -4.71 (-6.72, -2.70), p<0.001
15.67% 16.58%
-60
-40
-20
0
LFC
relative
change
from
baseline
(%)
-29.78†††
-47.11†††
-39.59†††
-11.17†
ETD -18.61 (-34.17, -3.04), p=0.019
ETD -28.42 (-43.85, -13.00), p<0.001
ETD -35.94 (-51.62, -20.27), p<0.001
Insulin
Degludec
TZP
5 mg
TZP
10 mg
TZP
15 mg
14.86% 14.78% 16.65% 16.58%
50. MRI Scan: Male, 59 Years, on Metformin + SGLT-2i
Randomised to Tirzepatide 5 mg
Abbreviations: BMI = body mass index; FSG = fasting serum glucose; HbA1c = haemoglobin A1c; LFC = liver fat content; SGLT-2i = sodium-glucose co-transporter-2 inhibitor; WC = waist circumference.
At Week 52
At Baseline
LFC
(%)
LFC
(%)
27.3
2.6
BMI: 44.8 kg/m2; body weight: 134.2 kg; WC: 139.7 cm
HbA1c: 78.1 mmol/mol (9.3%)
FSG: 10.3 mmol/L (186 mg/dL)
BMI: 36.2 kg/m2; body weight: 108.4 kg; WC: 124.4 cm
HbA1c: 43.2 mmol/mol (6.1%)
FSG: 5.9 mmol/L (107 mg/dL)
51. SURPASS-4
Efficacy and Safety of
Tirzepatide Once Weekly
Versus Insulin Glargine
in Patients with Type 2
Diabetes and Increased
Cardiovascular Risk
SURPASS-4
52. Key Inclusion Criteria
♦ T2D
♦ HbA1c ≥7.5% to ≤10.5%
♦ BMI ≥25 kg/m2
♦ Increased CV risk
♦ Use of 1-3 OAMs:
• metformin
• SGLT-2i
• sulfonylurea
Key Exclusion Criteria
♦ T1D
♦ History of pancreatitis
♦ Prior insulin use
Study Design
c The starting dose of insulin glargine will be 10 IU/day at bedtime, titrated to a FBG <5.6 mmol/L (100 mg/dL), following a treat-to-target algorithm (Riddle et al. 2003).
Study End Criteria
♦ ≥ 52 weeks for all
♦ ≥78 weeks for ≥300 on tirzepatide
♦ ~110 having MACE-4
SURPASS-4
53. HbA1c and FSG Change Over Time
mITT population (efficacy analysis set). Data are LSM (SE) over time, MMRM analysis up to 104 weeks. Arrows indicate time of primary endpoint. Dashed lines show baseline
values and dotted lines target values.
Tirzepatide 5 mg
Tirzepatide 10 mg
Tirzepatide 15 mg
Insulin Glargine
SURPASS-4
54. Body Weight Over Time
mITT population (efficacy analysis set). Data are LSM (SE) over time, MMRM analysis up to 104 weeks. Arrow indicates time of primary endpoint. Dashed line shows baseline value.
Tirzepatide 5 mg
Tirzepatide 10 mg
Tirzepatide 15 mg
Insulin Glargine
SURPASS-4
55. Lipid Profile at 52 Weeks and Over Time
mITT population (efficacy analysis set). Data are LSM (SE) at 52 weeks and up to 104 weeks from MMRM
analysis using log transformation. *p<0.001 vs. insulin glargine. Arrows indicate time of primary endpoint.
Tirzepatide 5 mg
Tirzepatide 10 mg
Tirzepatide 15 mg
Insulin Glargine
56. Blood Pressure Over Time
mITT population (safety analysis set). Data are LSM (SE) from MMRM analysis. Arrows indicate time of primary endpoint. Dashed lines show baseline values.
Systolic Blood Pressure Diastolic Blood Pressure
Tirzepatide 5 mg
Tirzepatide 10 mg
Tirzepatide 15 mg
Insulin Glargine
57.
58.
59. Tirzepatide, a Dual GIP/GLP-1
Receptor Agonist, is Effective
and Safe When Added to Basal
Insulin for Treatment of Type 2
Diabetes (SURPASS-5)
Dominik Dahl1, Yukiko Onishi2, Paul Norwood3, Ruth
Huh,4 Hiren Patel,4 Angel Rodriguez4
1Gemeinschaftspraxis für Inner Medizin und
Diabetologie, Hamburg, Germany, 2The Institute of
Medical Science, Asahi Life Foundation, Tokyo, Japan,
3Endocrine and Research, Fresno, USA, 4Eli Lilly and
Company, Indianapolis, USA
European Association for the Study of Diabetes, 57th Annual Meeting; Virtual; 27 September - 01 October, 2021
Oral Presentation: 20
SURPASS-5
60. Study Design
Participating Countries:Czech Republic, Germany, Japan, Poland, Puerto Rico, Slovakia, Spain, and the United States.
aRestricted insulin dose adjustments
Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA = haemoglobin A ; QW = once-weekly.
Key Inclusion Criteria
■ Type 2 diabetes
■ HbA1c ≥7.0% to ≤10.5% at screening
■ BMI ≥23 kg/m2 with stable weight
■ On stable dose of once-daily insulin
glargine (>0.25 U/kg/day or >20 U/day)
with or without metformin 3 months prior
to screening
■ Require further insulin glargine dose
increase at randomization
Key Exclusion Criteria
■ Type 1 diabetes
■ History of pancreatitis
■ eGFR <30 mL/min/1.73 m2
(<45 mL/min/1.73 m2 if on metformin)
Randomised, double-blind, placebo-controlled, parallel group, multicenter, multinational trial
SURPASS-5
61. HbA1c
Tirzepatide 5 mg Tirzepatide 15 mg
Tirzepatide 10 mg Placebo
Data on left panel are LSM (SE); MMRM analysis. Data on right panel are estimated proportion; Logistic regression. mITT (efficacy analysis set). Arrows on X-axis in overtime plot indicate
when maintenance doses of tirzepatide 5 mg, 10 mg, and 15 mg were achieved. **p<0.001 vs placebo. Estimated treatment difference in mean change from baseline in HbA1c (95% CI) of
tirzepatide vs. placebo was (i) tirzepatide 5 mg: -14.2** (-16.6, -11.7), (ii) tirzepatide 10 mg: -18.1** (-20.6, -15.7); and (iii) tirzepatide 15 mg: -18.1** (-20.5, -15.6).
Abbreviations: CFB = change from baseline; CI = confidence interval; HbA1c = glycated haemoglobin A1c; LSM = least squares mean; mITT = modified Intent-to-Treat; MMRM = mixed model
repeated measures; SE = standard error.
HbA1c Overtime and Change from
Baseline at Week 40
% Participants Achieving HbA1c
Goals at Week 40
0
20
40
60
80
100
Proportion
of
participants
(%)
HbA1c <53 mmol/mol
(<7.0%)
HbA1c ≤48 mmol/mol
(≤6.5%)
HbA1c <39 mmol/mol
(<5.7%)
**
93
**
97
**
94
34
**
80
**
95
**
92
17
**
26
**
48
**
62
3
SURPASS-5
62. Body Weight
Body Weight Overtime and Change from Baseline at Week 40
Data on left panel are LSM (SE); MMRM analysis. Data on right panel are estimated proportion; Logistic regression. mITT (efficacy analysis set). Arrows on X-axis in overtime plot indicate when maintenance doses of tirzepatide 5 mg, 10 mg, and 15 mg were
achieved. *p<0.05, **p<0.001 vs placebo at Week 40. Estimated treatment difference (95% CI) of tirzepatide vs. placebo for mean change from baseline in weight at Week 40 was (i) tirzepatide 5 mg: -7.8** (-9.4, -6.3), (ii) tirzepatide 10 mg: -9.9** (-11.5, -8.3); and
(iii) tirzepatide 15 mg: -12.6** (-14.2, -11.0).
Abbreviations: CFB = change from baseline; CI = confidence interval; LSM = least squares mean; mITT = modified Intent-to-Treat; MMRM = mixed model repeated measures; SE = standard error.
Tirzepatide 5 mg Tirzepatide 15 mg
Tirzepatide 10 mg Placebo
SURPASS-5
63. Insulin Glargine Dose
Data are estimated means (SE). MMRM analysis using log-transformed data, mITT efficacy analysis set. Arrows on X-axis in overtime plot indicate when maintenance doses of tirzepatide 5 mg, 10 mg, and 15 mg were achieved. **p<0.001 vs placebo at Week 40. For left panel, estimated placebo-
adjusted percent change (95% CI) vs. placebo was: (i) tirzepatide 5 mg: -35.4** (-46.0, -22.8), (ii) tirzepatide 10 mg: -38.2** (-48.3, -26.1); and (iii) tirzepatide 15 mg: -49.3** (-57.7, -39.4).
Abbreviations: CI = confidence interval; ETD = estimated treatment difference; mITT = modified Intent-to-Treat; MMRM = mixed model repeated measures; SE = standard error.
Change from baseline
(in IU/kg/day)
0.08 0.07 0.00 0.26
Insulin Glargine Dose
Percent Change from Baseline Overtime
Insulin Glargine Dose
Change from Baseline at Week 40
Tirzepatide 5 mg Tirzepatide 15 mg
Tirzepatide 10 mg Placebo
SURPASS-5
64. GPGN-SURPASS CVOT
42+12
I8F-MC-GPGN -The Effect of Tirzepatide versus
Dulaglutide on Major Adverse Cardiovascular Events
in Patients with Type 2 Diabetes (SURPASS-CVOT)
@CristobMorales
65. SURPASS CVOT: Versus dulaglutide 1.5 mg
A study to compare the effect of tirzepatide (maximum tolerated dose) vs dulaglutide 1.5 mg on major
cardiovascular events in participants with T2D with established CVD
SURPASS-CVOT. Available at: https://clinicaltrials.gov/ct2/show/NCT04255433. Accessed May 2020
0 4 8 12 16 20 24 28 32 36 40 44
Week -2 -1
Screening
Randomization
(Estimated enrolment: N=12,500)
(≥1615 events)
DU 1.5 mg QW
Up to TZP 15 mg QW
2.5
mg
5
mg
7.5
mg
10
mg
12.5
mg
15
mg
Dose Escalation Period Maintenance Period
66. A Randomized, Phase 3, Open-label Trial Comparing the Effect of the Addition of
Tirzepatide Once Weekly versus Insulin Lispro (U100) Three Times Daily in
Participants with Type 2 Diabetes Inadequately Controlled on Insulin Glargine
(U100) with or without Metformin (SURPASS-6)Protocol Number:I8F-MC-GPHD
GPHD-SURPASS 6 VS LISPRO
11+3
CUALQUIER INSULINA BASAL ESTABLES 3M
(>30UI y >0,3 UI/KG/DÍA)
CON O SIN ADOS: MET /SU /DPP4 (NO SGLT2)
A1C 7,5-11%
IMC ≥ 23 Kg/m2
NO RETINOPATÍA NO PROLIFERATIVA QUE REQUIERA TRATAMIENTO, NO
RP PROLIFERATIVA O EDEMA MACULAR
@CristobMorales
Speaker note:
The concept that hormones released by the intestine upon food intake potentiate nutrient-induced insulin secretion was identified in the early 1900’s. This phenomenon was later named the incretin effect, in the 30’s. Although the term incretin refers to any intestinal hormone that stimulate insulin release upon food intake, it is now commonly used to refer specifically to GIP and GLP-1, the main intestinal hormones responsible for the incretin effect under physiological circumstances.
Abbreviations:
GIP = glucose-dependent insulinotropic polypeptide; GLP-1 = glucagon-like peptide-1.
References:
Orskov C, Holst JJ, Knuhsten S, et al. Glucagon-Like Peptides GLP-1 and GLP-2, Predicted Products of the Glucagon Gene, Are Secreted Separately from Pig Small Intestine but Not Pancreas. Endocrinol. 1986;119(4):1467-1475.
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696-1705.
Aronoff SL, Berkowitz K, Shreiner B, et al. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectr. 2004;17(3):183-190.
Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev. 2008;60(4):470-512.
Abbreviations
GIP = glucose-dependent insulinotropic polypeptide; GLP-1 = glucagon-like peptide-1.
Speaker notes
This is the molecule now in phase 3 of development
Tirzepatide (LY3298176) is a 39 amino acid linear peptide and includes a C20 fatty acid. This will allow the binding of the molecule to albumin and prolongation of its half-life
The molecular weight is 4.8 kD
It is a multi-functional peptide based on the native GIP peptide sequence that was modified to bind to both GIP and GLP-1 receptors
In vitro, it has higher potency to native GIP and is less potent to native GLP-1
The mean half-life is of approximately 5 days (116.7 h), and this enables once-weekly dosing
Now, let’s spend a few minutes with some of these characteristics
References
Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub October 3, 2018. PMID: 30473097; PMCID: PMC6308032.
Abbreviations
cAMP, cyclic adenosine monophosphate; GIP, glucose-dependent insulinotropic polypeptide; GIPR, glucose-dependent insulinotropic polypeptide receptor; GLP-1, glucagon-like peptide-1; GLP-1R, glucagon-like peptide-1 receptor; PoC, proof of concept; T2D, type 2 diabetes; TZP, tirzepatide
Speaker notes
Prior to administration to healthy volunteers and people with T2D in the Phase 1/1b PoC study, tirzepatide was characterised in vitro
In signaling studies using cell lines recombinant for GIPR or GLP-1R, tirzepatide potently stimulated cAMP accumulation, an indirect way to measure binding to either receptor
Reference
Coskun T, et al. Mol Metab 2018;18:3-14
Speaker notes:
SURPASS-1 is a double-blind, randomized, placebo-controlled trial assessing the glycemic efficacy and safety of 3 doses of tirzepatide (TZP) once weekly (QW) (5, 10, and 15 mg) as monotherapy vs. placebo in people with type 2 diabetes (T2D) inadequately controlled with diet and exercise alone and naïve to injectable diabetes therapy1
The primary objective is superiority of TZP 5 mg and/or 10 mg and/or 15 mg vs. placebo in mean change in glycated hemoglobin (HbA1c) from baseline at 40 weeks
SURPASS-2 is a randomized, open-label, active-controlled, parallel-group trial comparing the efficacy and safety of TZP 5, 10, and 15 mg vs. semaglutide 1 mg in patients with T2D inadequately controlled on metformin monotherapy2
The primary objective is noninferiority of TZP vs. semaglutide in mean HbA1c change from baseline at 40 weeks
SURPASS-3 is a randomized, active-controlled, open-label, parallel-group trial investigating the effects on glycemic control, body weight, and safety of TZP QW 5, 10, and 15 mg compared with titrated once-daily insulin degludec in patients with T2D with inadequate glycemic control on a stable dose of metformin with or without sodium-glucose co-transporter-2 inhibitor (SGLT2i)3
The primary efficacy endpoint is noninferiority of TZP 10 and/or 15 mg vs. insulin degludec in mean change from baseline in HbA1c at 52 weeks
SURPASS-4 is a randomized, parallel, open-label trial comparing the efficacy and safety of TZP 5, 10, and 15 mg to insulin glargine in adults with T2D inadequately controlled with at least 1 and up to 3 oral antihyperglycemic medications (OAMs) (metformin, sulfonylureas, or SGLT2is), who have increased cardiovascular (CV) risk4
The primary objective of the study is to demonstrate that TZP (10 and/or 15 mg) is noninferior to insulin glargine for change from baseline HbA1c at 52 weeks in people with T2D and increased CV risk
The primary and key secondary endpoints were assessed at 52 weeks, with some participants continuing treatment for up to 2 years
SURPASS-5 is a double-blind, placebo-controlled trial assessing efficacy and safety of TZP (5, 10, and 15 mg) as an add-on to titrated insulin glargine with or without metformin vs. placebo in people with T2D5
The primary objective is to demonstrate that TZP 10 and 15 mg when added to titrated insulin glargine are superior to placebo in HbA1c change from baseline to 40 weeks
Abbreviations:
HbA1c = glycated hemoglobin; QW = once weekly; TZP = tirzepatide.
References:
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Eng J Med. 2021;385(6):503-515.
Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial Lancet. 2021;398(10300):583-598.
Del Prato S, Kahn SE, Pavo I, et al. Once-weekly tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;(Accepted).
Dahl D, Onishi Y, Norwood P et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Poster presented at the 81st Scientific Sessions of the American Diabetes Association. June 25-29, 2021. Poster LB-20.
Abbreviations:
OAM = oral antihyperglycemic medication; SGLT2i = sodium-glucose co-transporter-2 inhibitor; SU = sulfonylurea; TID = three times daily; T2D = type 2 diabetes.
References:
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes N Eng J Med. 2021;385(6):503-515.
Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598.
Del Prato S, Kahn SE, Pavo I, et al. Once-weekly tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;(Accepted).
Dahl D, Onishi Y, Norwood P, et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Poster Presented at the 81st Scientific Sessions of the American Diabetes Association. June 25-29, 2021. Poster LB-20.
ClinicalTrials.gov. A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6). Available at: https://clinicaltrials.gov/ct2/show/NCT04537923 (Accessed August 17, 2021).
ClinicalTrials.gov. A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT). Available at: https://clinicaltrials.gov/ct2/show/NCT04255433 (Accessed August 17, 2021).
Abbreviations: BMI = body mass index; CV= cardiovascular; FBG = fasting blood glucose; HbA1c = hemoglobin A1c; MACE = major adverse cardiovascular events; OAM = oral antihyperglycemic medication; QD = once-daily; QW = once-weekly; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU=sulfonylurea; T1D = type 1 diabetes; T2D = type 2 diabetes.
Figure Footnotes:
a Patients will be on study drug for at least 12 months and will receive no more than 24 months of treatment.
b All patients will perform a Visit 801 4 weeks after their last treatment visit.
c The starting dose of insulin glargine will be 10 IU/day at bedtime, titrated to a FBG <100 mg/dL, following a TTT algorithm (Riddle et al. 2003).
d Patients will titrate insulin glargine dose in a weekly manner and will make the dose decision with the investigator for the first 8 weeks (phone or clinic visit). From Week 8 to Week 16, patients will continue the titration by a phone consultation or clinic visit every other week, with 3 weeks between Visits 13 and 14.
Speaker Notes:
Increased cardiovascular risk included: CAD, PAD, CVD, CKD, CHF
Insulin related exclusion criteria: history of insulin therapy except for the use of insulin for treatment of gestational diabetes or acute, temporary use of insulin (≤14 days), for example, for acute illness, hospitalization, elective surgery
Abbreviations: FSG = fasting serum glucose; HbA1c = hemoglobin A1c; LSM = least squares means; mITT population = modified Intent-to-Treat; MMRM = mixed model repeated measures; TZP = tirzepatide; SE = standard error.
Speaker Notes: Error bars not visible for all data points as are within the size of the symbols.
Abbreviations: LSM = least squares means; mITT = modified Intent-to-Treat; MMRM = mixed model repeated measures; SE = standard error; TZP = tirzepatide.
Speaker Notes: Error bars not visible for all data points as are within the size of the symbols.
Abbreviations: LSM=least squares mean; mITT=modified-intent-to-treat; MMRM=mixed model repeated measures; safety analysis set = all available data obtained during Study Period II or II from mITT population, regardless of adherence to study drug or initiation of new antihyperglycemic medication; SE=standard error; SFU = safety follow-up; TZP = tirzepatide.
Abbreviations
BMI, body mass index; CV, cardiovascular; DU, dulaglutide; HbA1c, glycated hemoglobin; MACE, major adverse cardiovascular events; MTD, maximum tolerated dose; QW, once weekly; T2D, type 2 diabetes; TZP, tirzepatide;
Speaker notes
SURPASS-COVT is a Phase 3, event-driven, double-blind study in people with T2D and established CV disease at elevated risk for MACE
The study is investigating TZP (up to 15 mg) QW compared with DU (1.5 mg) QW
To compare the efficacy and safety of tirzepatide vs dulaglutide, the study is designed to last up 54 months, or until ≥1615 events are accrued
Criteria
Inclusion Criteria:
Have a diagnosis of type 2 diabetes
Have confirmed atherosclerotic cardiovascular disease
HbA1c ≥7.0% to ≤10.5%
BMI ≥25 kg/m²
Exclusion Criteria:
Have had a major cardiovascular event within the last 60 days
Have type 1 diabetes
Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the last 6 months
Have a history of proliferative diabetic retinopathy; or diabetic maculopathy; or non-proliferative diabetic retinopathy that requires acute treatment
Currently planning a coronary, carotid, or peripheral artery revascularization
Have a history of pancreatitis
Have a history of ketoacidosis or hyperosmolar state/coma
Have a known clinically significant gastric emptying abnormality, have undergone or plan to have during the course of the study, or chronically take drugs that directly affect gastrointestinal motility
Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years
Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
Reference
SURPASS-CVOT. Available at: https://clinicaltrials.gov/ct2/show/NCT04255433. Accessed May 2020
This visual representation does not establish clinical comparability nor allow a direct comparison of the SURPASS clinical trial results. Use caution when evaluating these results because of differences in study design, population, and key inclusion/exclusion criteria. Any conclusions are based on the subjective assessments of the presenter and serve purely as a basis for discussion.
Speaker note:
All 3 tirzepatide (TZP) doses provided superior glycated hemoglobin (HbA1c) reductions compared to placebo or active comparators in all 5 SURPASS trials
Additional information:
In SURPASS-3, all patients in the titrated insulin degludec treatment arm started with a baseline dose of 10 U/day and titrated once weekly to a fasting self-monitored blood glucose (SMBG) of <90 mg/dL (5.0 mmol/L). The mean dose of insulin degludec at 52 weeks was 48.8 U/day
In SURPASS-4, all patients in the titrated insulin glargine treatment arm started with a baseline dose of 10 U/day and titrated following a treat-to-target algorithm to reach fasting blood glucose (FBG) <100 mg/dL (5.6 mmol/L). The mean dose of insulin glargine at 52 weeks was 43 U/day
In SURPASS-5, baseline insulin glargine was 39.1 U/day, 34.7 U/day, 40.5 U/day, and 36.3 U/day for 5 mg, 10 mg, and 15 mg doses of TZP and placebo, respectively. The mean dose of insulin glargine at 40 weeks was 43.5 U/day, 37.4 U/day, 36.7 U/day, and 61.4 U/day for 5 mg, 10 mg, and 15 mg doses of TZP and placebo, respectively
Abbreviations:HbA1c = glycated hemoglobin; LSM = least squares mean; MET = metformin; mITT = modified intent-to-treat; MMRM = mixed model repeated measures; SEMA = semaglutide; SGLT2i = sodium-glucose co-transporter-2 inhibitor; SU = sulphonylurea; TZP = tirzepatide.
References:
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes N Eng J Med. 2021;385(6):503-515.
Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial Lancet. 2021;398(10300):583-598.
Del Prato S, Kahn SE, Pavo I, et al. Once-weekly tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;(Accepted).
Dahl D, Onishi Y, Norwood P et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Poster Presented at the 81st Scientific Sessions of the American Diabetes Association. 25-29 June 2021. Poster LB-20.
This visual representation does not establish clinical comparability nor allow a direct comparison of the SURPASS clinical trial results. Use caution when evaluating these results because of differences in study design, population, and key inclusion/exclusion criteria. Any conclusions are based on the subjective assessments of the presenter and serve purely as a basis for discussion.
Speaker note:
Between 81% and 97% of the participants treated with tirzepatide achieved the ADA-recommended HbA1c target of <7.0% (<53 mmol/mol)
Additional information:
In the SURPASS-3 trial, all patients in the titrated insulin degludec treatment arm started with a baseline dose of 10 U/day and titrated once weekly to a fasting self-monitored blood glucose (SMBG) of <90 mg/dL (5.0 mmol/L). The mean dose of insulin degludec at 52 weeks was 48.8 U/day
In the SURPASS-4 trial, all patients in the titrated insulin glargine treatment arm started with a baseline dose of 10 U/day and titrated following a treat-to-target algorithm to reach fasting blood glucose (FBG) <100 mg/dL (5.6 mmol/L). The mean dose of insulin glargine at 52 weeks was 43 U/day
In SURPASS-5, baseline insulin glargine was 39.1 U/day, 34.7 U/day, 40.5 U/day, and 36.3 U/day for 5 mg, 10 mg, and 15 mg doses of tirzepatide and placebo, respectively. The mean dose of insulin glargine at 40 weeks was 43.5 U/day, 37.4 U/day, 36.7 U/day, and 61.4 U/day for 5 mg, 10 mg, and 15 mg doses of tirzepatide and placebo, respectively
Abbreviations:
HbA1c = glycated hemoglobin; MET = metformin; mITT = modified intent-to-treat; SEMA = semaglutide; SGLT2i = sodium-glucose co-transporter-2 inhibitor; SU = sulphonylurea; TZP = tirzepatide.
References:
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes N Eng J Med. 2021;385(6):503-515.
Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial Lancet. 2021;398(10300):583-598.
Del Prato S, Kahn SE, Pavo I, et al. Once-weekly tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;(Accepted).
Dahl D, Onishi Y, Norwood P et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Poster Presented at the 81st Scientific Sessions of the American Diabetes Association. 25-29 June 2021. Poster LB-20.
This visual representation does not establish clinical comparability nor allow a direct comparison of the SURPASS clinical trial results. Use caution when evaluating these results because of differences in study design, population, and key inclusion/exclusion criteria. Any conclusions are based on the subjective assessments of the presenter and serve purely as a basis for discussion.
Speaker note:
Between 23% and 62% of patients treated with tirzepatide (TZP) achieved normoglycemia (glycated hemoglobin [HbA1c] <5.7% [<39 mmol/mol])
Additional information:
In the SURPASS-2 and SURPASS-5 trials, HbA1c <5.7% (39 mmol/mol), TZP 10 mg and 15 mg vs placebo were controlled for type 1 error, whereas TZP 5 mg was not controlled for type 1 error
In the SURPASS-3 trial, HbA1c <5.7% (39 mmol/mol) was not controlled for type 1 error
In the SURPASS-4 trial, HbA1c <5.7% (39 mmol/mol) was not controlled for type 1 error
In the SURPASS-3 trial, all patients in the titrated insulin degludec treatment arm started with a baseline dose of 10 U/day and titrated once weekly to a fasting self-monitored blood glucose (SMBG) of <90 mg/dL (5.0 mmol/L). The mean dose of insulin degludec at 52 weeks was 48.8 U/day
In the SURPASS-4 trial, all patients in the titrated insulin glargine treatment arm started with a baseline dose of 10 U/day and titrated following a treat-to-target algorithm to reach fasting blood glucose (FBG) <100 mg/dL (5.6 mmol/L). The mean dose of insulin glargine at 52 weeks was 43 U/day
In the SURPASS-5 trial, baseline insulin glargine was 39.1, 34.7, 40.5, and 36.3 U/day for 5, 10, and 15 mg doses of TZP and placebo, respectively. The mean dose of insulin glargine at 40 weeks was 43.5, 37.4, 36.7, and 61.4 U/day for 5, 10, and 15 mg doses of tirzepatide and placebo, respectively
Abbreviations:
HbA1c = glycated hemoglobin; MET = metformin; mITT = modified intent to treat; SEMA = semaglutide; SGLT2i = sodium-glucose co-transporter-2 inhibitor; SU = sulfonylurea; TZP = tirzepatide.
References:
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes N Eng J Med. 2021;385(6):503-515.
Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial Lancet. 2021;398(10300):583-598.
Del Prato S, Kahn SE, Pavo I, et al. Once-weekly tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;(Accepted).
Dahl D, Onishi Y, Norwood P et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Poster presented at the 81st Scientific Sessions of the American Diabetes Association. June 25-29, 2021. Poster LB-20.
This visual representation does not establish clinical comparability nor allow a direct comparison of the SURPASS clinical trial results. Use caution when evaluating these results because of differences in study design, population, and key inclusion/exclusion criteria. Any conclusions are based on the subjective assessments of the presenter and serve purely as a basis for discussion.
Speaker note:
All 3 tirzepatide doses provided superior reductions in body weight compared to the placebo or active comparator each of the SURPASS trials
Abbreviations:
LSM = least squares mean; MET = metformin; mITT = modified intent-to-treat; MMRM = mixed model repeated measures; SEMA = semaglutide; SGLT2i = sodium-glucose co-transporter-2 inhibitor; SU = sulphonylurea; TZP = tirzepatide.
References:
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes N Eng J Med. 2021;385(6):503-515.
Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial Lancet. 2021;398(10300):583-598.
Del Prato S, Kahn SE, Pavo I, et al. Once-weekly tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;(Accepted).
Dahl D, Onishi Y, Norwood P et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Poster Presented at the 81st Scientific Sessions of the American Diabetes Association. 25-29 June 2021. Poster LB-20.
Speaker note:
All tirzepatide doses were superior to semaglutide 1 mg for proportion of participants achieving all body weight loss goals at 40 weeks
Abbreviations:
mITT=modified intent-to-treat; MMRM=mixed model repeated measures; SEMA = semaglutide.
Reference:
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes N Eng J Med. 2021;385(6):503-515.