This document summarizes a clinical presentation on the basal insulin degludec and barriers to achieving optimal glycemic control. It discusses that hypoglycemia and glucose variability are barriers, and that current basal insulins have limitations like needing to be dosed at the same time daily and intra-patient variability. Insulin degludec was developed to address these barriers with properties like an ultra-long half-life of over 25 hours, very low day-to-day variability in glucose-lowering effect, and the ability to reach steady-state in 3 days. Large clinical trials showed degludec was as effective as glargine at reducing A1c and had a similar or lower risk of hyp
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
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
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
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Insulin Initiation : When We should Start with Basal Insulin?mataharitimoer MT
Insulin Initiation : When We should Start with Basal Insulin?
Dr. Agus Taolin , SpPD, FINASIM | PAPDI CABANG BOGOR
Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013
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.
On DPP-Inhibitor ,case study on Linagliptin,Safe and affective class of drug for Management of Type II Diabetes as Monotherapy and add on therapy with OHA and Insulin,It can be added to SGLT2 Inhibitor also.
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
Insulin Initiation : When We should Start with Basal Insulin?mataharitimoer MT
Insulin Initiation : When We should Start with Basal Insulin?
Dr. Agus Taolin , SpPD, FINASIM | PAPDI CABANG BOGOR
Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013
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.
On DPP-Inhibitor ,case study on Linagliptin,Safe and affective class of drug for Management of Type II Diabetes as Monotherapy and add on therapy with OHA and Insulin,It can be added to SGLT2 Inhibitor also.
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
Diabetese- One reason not to Worry ! A new Clinically researched NATURAL PROD...VISHAL CHANDRA
DBC-24 is a new researched product from TULIP LAB.
Clinical Trail has established good efficacy and safety of the product in lowering blood glucose levels and reducing insulin resistance with regular usage.
The product is devoid of side effects of Chemical based Drugs.
The product is also effective in management of Irregular menstrual cycle on account of Cyst formation in Ovaries
( Poly Cystic Ovarian Syndrome- PCOS )
International level clinical trail has been registered on WHO PORTAL : See the link in the slides
For
Transplantation of Autologous Bone Marrow- Derived Stromal Cells in Type 2 Di...CrimsonpublishersITERM
Type 2 Diabetes is a debilitating metabolic disorder which is also the seventh leading cause of death worldwide. Current therapeutic regimes to date have failed to achieve significant long-term glycemic control even with intensive insulin therapy as revealed by deregulated Hb1Ac and C-peptides levels. In the current study, we have evaluated the effect of regenerative cellular therapy for functional recovery from Diabetic pathophysiology. 10 patients with a median age of 51 years were selected for the study and subjected to bone marrow isolation. These samples were processed under sterile conditions for the enrichment of mononuclear cells (BM MNCs) from bone marrow. After strict quality control and characterization of cells, 2 x 106 cells/kg of BM MNCs were infused back into the patient through the anterior pancreaticoduodenal artery. We performed an evaluation of clinical parameters like Body Mass Index, Fasting Plasma Glucose, Fasting Plasma Insulin, HbA1c and C-peptide levels, and followed up the patients for 12 months. Our study showed a reduction in insulin dependency by ≥ 50%.
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
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.
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
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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.
- 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
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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
1. Addressing Barriers in Achieving Optimal
Glycemic Target with Ideal Basal Insulin,
Degludeg & its Clinical Experience in
Glycemic Control
1
Dr Shahjada Selim
Assistant Professor
Department of Endocrinology
BSMMU
2. Objectives
• To obtain insights on the existing insulin therapy
barriers and to understand the need for a better insulin
• To learn about the new ultra-long-acting basal insulin -
the molecule of Insulin Degludec
• Pharmacokinetics/Pharmacodynamics
• Clinical efficacy and safety
• Flexibility in dosing
• Clinical use, dosing and titration
4. Canada 7.36–8.7%11
Latin America 7.6%1
US 7.2%7
China 9.5%11
India 8.7–9.6%9,11
Japan 7.05–9.6%11
Korea 7.9–8.7%4
Russia 9.6%11
Spain 9.2%8
Sweden 8.7%3
Turkey 10.6%3
UK 8.510–9.8%2
Germany 8.42–9.2%8
Greece 8.911–9.7%3,8
Italy 8.4%11
Poland 9.0%11
Portugal 9.7%3
Romania 9.9%3
1. Lopez Stewart et al. Rev Panam Salud Publica 2007;22:12–20; 2. Kostev & Rathmann Primary Care Diabetes 2013;7:229–33; 3. Oguz et al. Curr Med Res Opin
2013;29:911–20; 4. Ko et al. Diabet Med 2007;24:55–62; 5. Arai et al. Diabetes Res Clin Prac 2009;83:397–401; 6. Harris et al. Diabetes Res Clin Pract 2005;70:90–7; 7.
Hoerger et.al. Diabetes Care 2008;31:81–6; 8. Liebl et al. Diabetes Ther 2012;3:e1–10; 9. Shah et al. Adv Ther 2009;26:325–35; 10. Blak et al. Diabet Med 2012;29:e13–20;
11. Valensi et al. Int J Clin Pract 2008;62:1809–19
Poor glycemic control:
A worldwide problem
Reported mean HbA1c in T2D patients exceeds local targets in nearly all countries
5. But why are we not getting to goal?
5
The glucose targets are known…
6. Patients have poor blood glucose control
Patients struggle to remain fully
compliant with their insulin regimens
Patients and physicians are concerned
about hypoglycemia
User friendly insulin regimens would
help empower patients and physicians
Insulin doses are being missed or not
taken as prescribed
Treatments are
needed that
respond to the
functional and
emotional
needs of people
with diabetes.
The need for
treatment
options that
could help
improve
compliance and
ultimately long
term health
outcomes.
Key global findings from the Survey
7. Barriers to achieving optimal glycemic
control
• Risk of Hypoglycemia
• Suboptimal dosing & titration
• Glucose Variability
Hypoglycemia
• Fear of Hypoglycemia
• Complexity of Regimen
• Lack of Flexibility
Adherence to
Treatment
8. Limitations with current basal insulin therapy
• Basal insulins must be administered
at the same time every day1
• Variability of glucose lowering
effect of current insulins (inter-
patient and intra-patient)2
• Currently available long-acting
insulin analogues do not always
last 24 hours2
• Reducing variability and
extending duration of action
could simplify titration and reduce
the incidence of hypoglycemia2
1. Joshi et al. SA Fam Pract 2009;51:97–102; 2. Evans et al. Diab Obesity Metab 2011;13:677–684
12. Hypoglycemia continues to be a problem with
current basal insulin analogues
12
1 of 4 patients on basal-only therapy had a
self-treated hypoglycemic event in the past 30 days
Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycemia in type 2 diabetes: a multinational survey in patients and physicians.
Current Medical Research and Opinion. 2012;28(12):1947-1958.
Percentage of patients who reported having at least one
self-treated hypoglycemic event in the past 30 days
All
Basal
only
Basal
+bolus
36% 45%25%
13. Fear of hypoglycemia is a concern for patients
taking basal insulin analogues
15
Percentage of patients worried about experiencing
self-treated nocturnal hypoglycemia
Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycemia in type 2 diabetes: a multinational survey in patients and physicians.
Current Medical Research and Opinion. 2012;28(12):1947-1958.
42%
57% of patients reported being concerned about
the potential negative impact of nocturnal
hypoglycemic events on their long-term health
14. Risk of hypoglycemia affects dose of insulin
initiated by HCPs
16
Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycemia in type 2 diabetes: a multinational survey in patients and physicians.
Current Medical Research and Opinion. 2012;28(12):1947-1958.
Percentage of HCPs who adjust initial dose of insulin
due to risk of hypoglycemia
56%
42%
56%
Initiated patients on a
lower insulin dose than
recommended due to
risk of hypoglycemic
events
15. Glucose variability (GV) predicts hypoglycemia
risk before starting and during insulin therapy
Qu et al. Diab Tech Therapeutics 2012;14:1008–12
Numbers next to bars are p values
GV is therefore likely to be a significant player in overall
treatment success
16. Variability of FPG and cardiovascular mortality
10-year survival
Group 1 (8.5%)
Group 2 (14.8%)
Group 3 (27.7%)
1.0
0.7
0.6
0.5
0.0
0 2 4 6 8 10
Time (years)
0.8
0.9
Survival
probability
Mean CV of FPG*
Variability in blood glucose is an
independent risk factor for mortality
*Significant differences in the CV of FPG (p<0.001)
Muggeo et al. Diabetes Care 2000;23:45–50
18. Need for an ideal basal insulin
What is Insulin Degludec?
20
19. Degludec:
Multi-hexamer formation key
to protraction mechanism
Degludec molecules form
hexamers
The side chain (linker) forms an accurate
fit between Degludec hexamers to form
multi-hexamers
20. Degludec association
Proposed steps from injection
to absorption
Degludec multi-hexamers
Degludec monomers
-Zn2+
Degludec di-hexamers
-Phenol
Injected
formulation
S.C. depot
formation
Absorption
22. PK/PD in T1DM: Half-life greater than
25 hours
24
2x longer half-life vs insulin glargine
(25.4 hours vs 12.5 hours)
Heise T, Hövelmann U, Nosek L, Bøttcher S, Granhall C, Haahr H. Insulin degludec has a two-fold longer half-life and a more consistent
pharmacokinetic profile than insulin glargine. Poster presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011;
San Diego, California, USA.
23. PK/PD in T1DM: Four times less variability
in glucose-lowering effect over 24 hours
vs insulin glargine
25
Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin
glargine under steady-state conditions in type 1 diabetes. Diabetes, Obesity and Metabolism. 2012;14(9):859-864.
GIR=glucose infusion rate; AUC GIR (GIR in subscript) =Area under the curve for glucose infusion rate; CV%= coeffecient of variation
24. Insulin degludec provides four times lower day-
to-day variability vs insulin glargine
Mean within-subject variability at steady state*
Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin
glargine under steady-state conditions in type 1 diabetes. Diabetes, Obesity and Metabolism. 2012;14(9):859-864.
4x less variability with insulin degludec vs insulin glargine
25. PK/PD in Type 2 DM: A flat, stable
glucose-lowering effect
27Insulin degludec [summary of product characteristics]. Bagsværd, Denmark: Novo Nordisk A/S; 2012.
GIR, glucose infusion rate
26. PK/PD in T2DM: Concentration reaches steady
state in 3 days
54320 1 6
Days since first dose
SerumIDegconcentration
ProportionofDay6level(%)
120
110
100
90
80
70
60
50
40
30
20
10
0
T2D
0 1 2 3 4
SerumIDegconcentration
ProportionofDay4level(%)
120
110
100
90
80
70
60
50
40
30
20
10
0
Days since first dose
T1D
T1D trial, n=66; T2D trial, n=49
T1D trial, 0.4, 0.6 or 0.8 U/kg; T2D trial, 0.4, 0.6 or 0.8 U/kg
Estimated ratios and 95% CI
Heise et al. Diabetes 2012;61(Suppl. 1):A259
27. Reaching steady state with insulin degludec
Units added each day
Units remaining
from prior
injections
(t1/2~24 h) Units absorbed into circulation
5 UDay 1 10 U
~9 U
7.5 U5 U
7.5 U
~9 U
10 U
10 U
15 U
17.5 U
19 U
20 U
10 U
10 UDay 5
Day 4
Day 3
Day 2
Insulin in s.c. depot
10 U
5050%
5050%
5050%
5050%
5050%
Insulin in circulationInjected insulin
Maximum units
present in 24h
interval
10 U
10 U
10 U
10 U
Therefore
there is no
stacking
Figure adapted from Heise and Meneghini Endocr Pract 2014;20:75–83
28. Pharmacokinetics of insulin degludec in special
populations Age
Hepatic function
Renal function
Geriatric (≥65)
Younger adults (18–35)
The PK properties of insulin
degludec are not affected by
increasing age, renal
impairment or hepatic
impairment
0
2000
4000
6000
8000
10000
0 4 8 12 16 20 24
IDegconcentration
(pmol/L)
Time since injection (hours)
Normal
Mild
Moderate
Severe
0
2000
4000
6000
8000
10000
0 4 8 12 16 20 24
IDegconcentration
(pmol/L)
Time since injection (hours)
Normal
Child-Pugh A
Child-Pugh B
Child-Pugh C
0 4 8 12 16 20 24
Time since injection (hours)
2000
4000
6000
8000
10000
IDegconcentration(pmol/L)
0
PK, pharmacokinetic
Kupčová et al. Clin Drug Investig 2014;34:127–33; Kiss et al. Clin Pharmacokinet 2014;53:175–83; Korsatko et al. Drugs Aging 2014;31:47–53
29. 31
Efficacy in reaching the target HbA1c
How well does IDeg achieve
glycemic control for patients?
30. 32
BEGIN™ phase 3 program
Investigating the efficacy and safety of Insulin
Degludec in type 1 and type 2 diabetes
32. Regulatory guidance recommends that insulin be tested in
a treat-to-target design:
BEGIN™ program designed to meet
noninferiority insulin trial standards
34
Center for Drug Evaluation and Research. Guidance for industry: diabetes mellitus: developing drugs and therapeutic biologics for treatment and
prevention (draft guidance). Rockville, MD: Food and Drug Administration, U.S. Dept of Health and Human Services; February 2008.
33. Summary of insulin degludec BEGIN™ phase 3
program
35
Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Ocampo Francisco AM, Pei H, Bode B. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin
aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012;379(9825):1489-1497; Data on file NN1250-3770. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo
Nordisk for additional information; Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-
target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-2471; Data on file NN1250-3672. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional information; Meneghini L, Atkin SL, Bain S, Gough S, Raz I, Blonde
L, Begtrup K, Johansen T, Birkeland KI. Flexible once-daily dosing of insulin degludec does not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes. Abstract
presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011; San Diego, California, USA. Abstract 35-LB; Data on file NN1250-3668. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional
information; Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Ocampo Francisco AM, Hollander P. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with
mealtime insulin aspart in type 2 diabetes. Lancet. 2012;379(9825):1498-1507; Onishi Y, Park SW, Yoo SJ, Clauson P, Tamer SC, Iwamoto Y. Insulin degludec improves glycemic control in insulin-naïve patients with type 2 diabetes: results of a
randomized pan-Asian trial. Poster presented at: 72nd Scientific Sessions of the American Diabetes Association; 8-12 June 2012; Philadelphia, Pennsylvania, USA. 1059-P.
OAD=oral anti-diabetic drug; MET=metformin; DPP-4=dipeptidyl peptidase-4
inhibitor; SU=sulphonylurea; TZD=thiazolidinedione.
35. Insulin-naïve T2D: study design
BEGIN ONCE LONG – 2 years
IDeg OD + metformin
± DPP-4 (n=773)
IGlar OD + metformin
± DPP-4 (n=257)
Insulin-naïve
patients with
type 2 diabetes
(n=1030)
Inclusion criteria
• Type 2 diabetes ≥6
months
• Insulin naïve, treated with
metformin ± SU, DPP-4 or
acarbose for ≥3 months
• HbA1c 7.0–10.0%
• BMI ≤40 kg/m2
• Age ≥18 years
Randomised 3:1 (IDeg OD: IGlar OD)
*1 week wash-out (week 52) to allow for antibody measurement, hence
105 weeks = 104 weeks’ exposure
Continue core phase
treatment (n=551)
Continue core phase
treatment (n=174)
Core phase – 52 weeks Extension phase – 52 weeks
105 weeks0 52* 53
OD, once daily
Zinman et al. Diabetes Care 2012;35:2464–71; Rodbard et al. Diabet Med 2013;30:1298–304
36. Equivalent reductions in HbA1c vs insulin
glargine
38
Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in insulin-
naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-2471.
37. Significant reductions in FPG vs insulin
glargine
39
Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in
insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-2471.
38. Significantly lower risk of nocturnal
hypoglycemia vs insulin glargine
40
• 36% lower risk of nocturnal confirmed hypoglycemia vs insulin glargine (P=0.038)
• 86% lower risk of severe hypoglycemia vs insulin glargine (P=0.017)
• 18% lower risk of overall confirmed hypoglycemia vs insulin glargine (P=NS)
Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in
insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-2471.
40. Patients are not taking basal insulin
as prescribed
42
Brod M, Rana A, Barnett AH. Adherence patterns in patients with type 2 diabetes on basal insulin analogues: missed, mistimed and
reduced doses. Current Medical Research and Opinion. 2012;28(12):1933-1946.
Percentage of patients reporting at least one basal
insulin dosing irregularity in the past 30 days
Almost 1 of 4 patients have mistimed* at least
one basal insulin dose in the past 30 days
22%
14%
24%
Missed
a dose
Mistimed
a dose
Reduced
a dose
*by ±2 hours from prescribed time.
41. 33.2% of patients
reported insulin omission ⁄
non-adherence at least 1
day in the last month,
with an
average of 3.3 days
73%
27%
67%
33%
73% of physicians reported
that their typical patient
does not take their insulin
as prescribed
Insulin doses are being missed or not taken as
prescribed
Too busy
18.9%
Travelling
16.2%
Challenging to
take at same
time each day
9.4%
Forgot
7.4%
Regimen too
complicated
3.8%
Peyrot et al. Diabet Med 2012;29:682–9
GAPP™
• A global internet
survey of patient
and physician
beliefs regarding
insulin therapy
• n=1250
physicians
43. Fixed administration time for basal insulin is difficult for
patients
1. Peyrot et al. Diabetic Medicine 2012;29:682–9; 2. Peyrot et al. Diabetes Care 2010;33:240–5
22% of patients said they planned
their daily activities around insulin
injections2
28% of patients said they find it
difficult to take insulin at the
prescribed time daily or with meals
every day1
44. 2-in-5 patients had missed a dose of
basal insulin within the last 30 days
Basal insulin
Missed, mis-timed (by more than 2 hours)
and reduced doses of basal insulin
Data on file.
Insulin analogue patients
45. 44% I had skipped a meal
39% I had exercised recently
81% I had exercised recently
71% I had skipped a meal
37% I had exercised recently
31% I had skipped a meal
On the last occasion that patients had missed, mis-
timed or reduced their basal insulin dose, 37%, 21%
and 68% (respectively) had done so intentionally
Proportion of patients intentionally
missing, mistiming or reducing a dose of
basal insulin the last time they did this
TOP 2 reasons for intentionally missing,
mistiming or reducing a dose of basal
insulin the last time they did this
Basal insulin
Insulin analogue patients
Data on file.
47. Insulin degludec and flexibility in
day-to-day dosing time
On occasions when administration at the same time of the
day is not possible, insulin degludec allows for flexibility in
the timing of insulin administration. A minimum of 8 hours
between injections should always be ensured.
Patients who forget a dose are advised to take it
upon discovery and then resume their usual once-
daily dosing schedule.
Insulin degludec [summary of product characteristics]. Bagsværd, Denmark: Novo Nordisk A/S; 2012. 51
49. Flexible vs Fixed dosing in T2D: study design
BEGIN FLEX T2D
Inclusion criteria
• Type 2 diabetes ≥6 months
• Previously treated with
OADs and/or basal insulin
• HbA1c:
OADs only 7–11%
Basal insulin ± OADs 7–10%
• BMI ≤40 kg/m2
• Age ≥18 years
Patients with
type 2 diabetes
(n=687)
0 26 weeks
Open label
IGlar OD ± OADs (n=230)
(metformin/SU/pioglitazone)
IDeg Fixed OD ± OADs (n=228)
(metformin/SU/pioglitazone)
IDeg Flexible OD ± OADs (n=229)
(metformin/SU/pioglitazone)
Meneghini et al. Diabetes Care 2013;36:858–64
50. Flexible dosing time
Mon Tue Wed Thu Fri Sat Sun
MorningMorning Morning
Evening Evening Evening Evening
40 h 40 h 40 h
8 h 8 h
24 h
Insulin degludec: Varied daily dosing
intervals (between 8 to 40 hours)
Insulin glargine: Dosed once daily at
the same time each day, per insulin
glargine label
Insulin degludec’s ultra-long duration of action and steady-state profile allows for a forced
flexible dosing interval in patients with diabetes
55
Meneghini L, Atkin SL, Bain S, Gough S, Raz I, Blonde L, Begtrup K, Johansen T, Birkeland KI. Flexible once-daily dosing of insulin degludec does
not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes.
Abstract presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011; San Diego, California, USA. Abstract 35-LB.
51. Summary of insulin degludec flexible
day-to-day dosing time
• Insulin degludec administered at flexible dosing times provided:
– Effective glycemic control with noninferior HbA1c reductions
compared to insulin glargine, with less nocturnal hypoglycemia
– FPG reductions greater than insulin glargine in patients with
type 2 diabetes
56
Meneghini L, Atkin SL, Bain S, Gough S, Raz I, Blonde L, Begtrup K, Johansen T, Birkeland KI. Flexible once-daily dosing of insulin degludec does
not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes.
Abstract presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011; San Diego, California, USA. Abstract 35-LB.
52. Flexibility in day-to-day dosing time
57
Establishing a routine is important, but it is not always possible to inject at
the same time each day…
On occasions when administration at the same time of day is not possible,
insulin degludec allows for flexibility in the timing of insulin administration
53. Who could benefit from flexibility in day-to-
day dosing time?
Juggles a busy
family life
Travels
Needs help
injecting
Has unpredictable
work hours
58
54. 59
Ideal
Basal
Insulin
Longer
duration
of action
Controls fasting
blood glucose with
1 injection per day
in all individuals
Has a long
duration of action
(at least 42 hours)
& a half-life twice
as long as that of
insulin glargine
Flat time-
action
profile
Lower risk of
hypoglycemia
Provides a flat and
stable glucose-
lowering effect,
equally distributed
over 24 hours
Less day-
to-day
variability
Lower hypo- and
hyperglycemia
Has 4 times lower
variability in
glucose-lowering
effect compared
with insulin
glargine
Ideal
Basal
Insulin
Clinical
Benefit
Insulin
Degludec
Improved Adherence &
Overall Glycemic Control
55. 60
Controls fasting
blood glucose with 1
injection per day in
all individuals
Has a long duration
of action (at least 42
hours) & a half-life
twice as long as that
of insulin glargine
Lower risk of
hypoglycemia
Provides a flat and
stable glucose-
lowering effect,
equally distributed
over 24 hours
Lower hypo- and
hyperglycemia
Has 4 times lower
variability in
glucose-lowering
effect compared
with insulin glargine
Clinical
Benefit
Insulin
Degludec
Improved Adherence &
Overall Glycemic Control
Lower risk of
complications Improve
Quality of
Life
57. PG <3.1 mmol/La
(56 mg/dL)
Yes
Hypoglycemia classification – consistent and
stringent in phase 3
Suspected hypoglycemia or
routine PG measurement
Patient able
to treat
self? No
Severe
hypoglycemia
Not classified as
confirmed hypoglycemia
Yes
Confirmed hypoglycemia
(including night time)
No
a: With or without symptoms
A nocturnal episode is any confirmed episode with time of onset between 00:01 am and 05:59 am, inclusive.
58. 0.25 0.5 1 2 4
Pre-specified meta-analyses: overall confirmed
hypoglycemia
In favour of IDeg In favour of IGlar
1.10 [0.96;1.26] Not significant
0.91 [0.83;0.99] Significant*
0.83 [0.70;0.98] Significant*
0.83 [0.74;0.94] Significant*
T2D
LOW VOLUME
BB
FLEX T2D
ONCE ASIA
ONCE LONG
Pooled T2D
FLEX T1D
BB T1D LONGT1D
Pooled T1D
Pooled T1D & T2D
52
26
26
26
52
52
26
Pooled insulin-naïve T2D
Weeks
Adjusted for trial, type of diabetes, anti-diabetes therapy at screening, sex, region and age. Flexible arm not included in analysis. *Significantly lower risk based on 95% CI
Ratner et al. Diabetes Obes Metab 2013;15:175–84
59. 0.25 0.5 1 2 4
Pre-specified meta-analyses: nocturnal
confirmed hypoglycemia
0.83 [0.69;1.00] Not significant
0.74 [0.65;0.85] Significant*
0.64 [0.48;0.86] Significant*
0.68 [0.57;0.82] Significant*
T2D
LOW VOLUME
BB
FLEX T2D
ONCE ASIA
ONCE LONG
Pooled T2D
FLEX T1D
BB T1D LONGT1D
Pooled T1D
Pooled T1D & T2D
26
26
26
52
52
26
Pooled insulin-naïve T2D
In favour of IDeg In favour of IGlar
52
Weeks
Adjusted for trial, type of diabetes, anti-diabetes therapy at screening, sex, region and age. Flexible arm not included in analysis. *Significantly lower risk based on 95% CI
Ratner et al. Diabetes Obes Metab 2013;15:175–84
60. Meta-analyses: severe hypoglycemia in type 1
and type 2 diabetes
0.03125 0.0625 0.125 0.25 0.5 1 2 4 8
Significant*0.14 [0.03;0.70]
Not significant0.81 [0.42;1.56]
Not significant1.12 [0.68;1.86]
Not significant0.97 [0.66;1.44]
In favour of IDeg In favour of IGlar
T2D
Pooled T2D
T1D Pooled T1D
Pooled T1D & T2D
Pooled insulin
-naïve T2D
Adjusted for trial, type of diabetes, anti-diabetes therapy at screening, sex, region and age. Flexible arm not included in analysis. *Significantly lower risk based on 95% CI
Ratner et al. Diabetes Obes Metab 2013;15:175–84
61. Nocturnal confirmed hypoglycemia
Definition
0.0 0.2 0.4 0.6 0.8 1 1.2 1.4
T2D Insulin-naïve
0.64 [0.48; 0.86]*
0.56 [0.39; 0.80]*
0.73 [0.56; 0.97]*
Nocturnal confirmed hypoglycemia
(original definition) (0:01–5:59)
Nocturnal confirmed symptomatic
hypoglycemia (0:01–5:59)
Nocturnal ADA documented symptomatic
hypoglycemia (0:01–5:59)
In favour of IDeg In favour of IGlar
0.51 [0.36; 0.72]*
0.43 [0.28; 0.64]*
0.62 [0.45; 0.84]*
0.75 [0.58; 0.99]*
0.68 [0.51; 0.91]*
0.72 [0.55; 0.93]*
0.72 [0.51; 1.00]
0.65 [0.45; 0.93]*
0.70 [0.51; 0.96]*
0.0 0.2 0.4 0.6 0.8 1 1.2 1.4
In favour of IDeg In favour of IGlar
Nocturnal confirmed hypoglycemia
(original definition) (0:01–5:59)
Nocturnal confirmed symptomatic
hypoglycemia (0:01–5:59)
Nocturnal ADA documented symptomatic
hypoglycemia (0:01–5:59)
T2D Basal–bolus
Entire trial period
Maintenance period only
Heller et al. Diabetes 2014;63(Suppl. 1):A106
62. Nocturnal confirmed hypoglycemia
Time period
0.0 0.2 0.4 0.6 0.8 1 1.2 1.4
T2D Insulin-naïve
0.64 [0.48; 0.86]*
0.60 [0.45; 0.80]*
0.93 [0.75; 1.15]
Nocturnal confirmed hypoglycemia
(original definition) (0:01–5:59)
Nocturnal confirmed hypoglycemia
(21:59–5:59)
Nocturnal confirmed hypoglycemia
(0:01–7:59)
In favour of IDeg In favour of IGlar
0.51 [0.36; 0.72]*
0.49 [0.35; 0.69]*
0.76 [0.59; 0.99]*
0.75 [0.58; 0.99]*
0.73 [0.59; 0.91]*
0.77 [0.60; 0.97]*
0.0 0.2 0.4 0.6 0.8 1 1.2 1.4
In favour of IDeg In favour of IGlar
Nocturnal confirmed hypoglycemia
(original definition) (0:01–5:59)
Nocturnal confirmed hypoglycemia
(21:59–5:59)
Nocturnal confirmed hypoglycemia
(0:01–7:59)
T2D Basal–bolus
0.72 [0.51; 1.00]
0.70 [0.54; 0.91]*
0.70 [0.53; 0.92]*
Entire trial period
Maintenance period only
Heller et al. Diabetes 2014;63(Suppl. 1):A106
63. Summary of efficacy and safety in
type 2 diabetes
• In patients with type 2 diabetes, insulin degludec provides
– Effective glycemic control with noninferior HbA1c reductions compared to insulin glargine,
with less hypoglycemia
– FPG reductions greater than insulin glargine
68
Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in
insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-
2471; Data on file NN1250-3672. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional information; Onishi Y, Park
SW, Yoo SJ, Clauson P, Tamer SC, Iwamoto Y. Insulin degludec improves glycemic control in insulin-naïve patients with type 2 diabetes: results of
a randomized pan-Asian trial. Poster presented at: 72nd Scientific Sessions of the American Diabetes Association; 8-12 June 2012; Philadelphia,
Pennsylvania, USA. 1059-P; Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Ocampo Francisco
AM, Hollander P. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in
type 2 diabetes. Lancet. 2012;379(9825):1498-1507.
OAD=oral anti-diabetic drug; MET=metformin; DPP-4=dipetidyl peptidase-4 inhibitor; TZD=thiazolidinedione.
64. Non-inferior HBA1c reduction & Significant
FPG reductions
69
Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Ocampo Francisco AM, Pei H, Bode B. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin
aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012;379(9825):1489-1497; Data on file NN1250-3770. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo
Nordisk for additional information; Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-
target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-2471; Data on file NN1250-3672. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional information; Meneghini L, Atkin SL, Bain S, Gough S, Raz I, Blonde
L, Begtrup K, Johansen T, Birkeland KI. Flexible once-daily dosing of insulin degludec does not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes. Abstract
presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011; San Diego, California, USA. Abstract 35-LB; Data on file NN1250-3668. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional
information; Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Ocampo Francisco AM, Hollander P. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with
mealtime insulin aspart in type 2 diabetes. Lancet. 2012;379(9825):1498-1507; Onishi Y, Park SW, Yoo SJ, Clauson P, Tamer SC, Iwamoto Y. Insulin degludec improves glycemic control in insulin-naïve patients with type 2 diabetes: results of a
randomized pan-Asian trial. Poster presented at: 72nd Scientific Sessions of the American Diabetes Association; 8-12 June 2012; Philadelphia, Pennsylvania, USA. 1059-P.
OAD=oral anti-diabetic drug; MET=metformin; DPP-4=dipeptidyl peptidase-4
inhibitor; SU=sulphonylurea; TZD=thiazolidinedione.
65. Significant reductions in hypoglycemia
70
Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Ocampo Francisco AM, Pei H, Bode B. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin
aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012;379(9825):1489-1497; Data on file NN1250-3770. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo
Nordisk for additional information; Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-
target trial (BEGIN™ Once Long). Diabetes Care. 2012;35(12):2464-2471; Data on file NN1250-3672. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional information; Meneghini L, Atkin SL, Bain S, Gough S, Raz I, Blonde
L, Begtrup K, Johansen T, Birkeland KI. Flexible once-daily dosing of insulin degludec does not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes. Abstract
presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011; San Diego, California, USA. Abstract 35-LB; Data on file NN1250-3668. Novo Nordisk A/S, Bagsværd, Denmark. Please contact Novo Nordisk for additional
information; Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Ocampo Francisco AM, Hollander P. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with
mealtime insulin aspart in type 2 diabetes. Lancet. 2012;379(9825):1498-1507; Onishi Y, Park SW, Yoo SJ, Clauson P, Tamer SC, Iwamoto Y. Insulin degludec improves glycemic control in insulin-naïve patients with type 2 diabetes: results of a
randomized pan-Asian trial. Poster presented at: 72nd Scientific Sessions of the American Diabetes Association; 8-12 June 2012; Philadelphia, Pennsylvania, USA. 1059-P.
OAD=oral anti-diabetic drug; MET=metformin; DPP-4=dipeptidyl peptidase-4
inhibitor; SU=sulphonylurea; TZD=thiazolidinedione.
66. Comparable reductions in nocturnal
hypoglycemia vs insulin glargine
71
• 23% lower risk of nocturnal confirmed hypoglycemia vs insulin glargine (P=NS)
• 3% higher risk of overall confirmed hypoglycemia vs insulin glargine (P=NS)
Meneghini L, Atkin SL, Bain S, Gough S, Raz I, Blonde L, Begtrup K, Johansen T, Birkeland KI. Flexible once-daily dosing of insulin degludec does
not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes.
Abstract presented at: 71st Scientific Sessions of the American Diabetes Association; 24-28 June 2011; San Diego, California, USA. Abstract 35-LB.
67. Who could benefit from hypoglycemia risk
reduction?
Reports
hypoglycemic events
Admits to lowering
dose to avoid
hypoglycemia
Is afraid of
hypoglycemia
Has higher fasting
target due to
hypoglycemia risk
72
69. Clinical Indications
• With intensified glucose monitoring and the insulin
dose adjusted on an individual basis, Insulin
Degludec can be used in:
Renal and Hepatic Impairment
Elderly (>65 years old)
• Safety and efficacy have not been established
in children and adolescents below 18 years of age.
• No clinical experience in pregnant women.
Animal reproduction studies have not revealed any
difference between Insulin Degludec and Human
Insulin regarding embryotoxicity and teratogenicity.
74
70. Dosing of Insulin Degludec
Initiation
Type 2 diabetes
• 10 units starting dose1
• Individual dose
adjustments1
Type 1 diabetes
• Combination with
mealtime insulin1
• Individual dose
adjustment1
Transfer from
other basal insulin
Type 2 diabetes
• Unit-to-unit switch from
prior basal
insulin/component1
Type 1 diabetes
• OD therapy: unit-to-unit
switch1
• BID basal insulin or HbA1c
<8.0%: dose determined on
an individual basis1
BID, twice daily
1. Tresiba® SmPC, Novo Nordisk, May 2013 75
71. How to adjust Insulin Degludec dose
once a week1
1. Get to steady state – typically 2–3 days after first dose
2. Titrate once-weekly based on average of 2 preceding FPG
measurements*
• ADA/EASD recommended FPG goal is 3.9 to 7.7 mmol/L (70
to 130 mg/dL) for many adult patients with diabetes2
22
FPG, fasting plasma glucose; ADA, American Diabetes Association; EASD, European Association for the
Study of Diabetes
If above goal, +2 units
If below goal, -2 units
If at goal, maintain dose
1. Tresiba® SmPC, Novo Nordisk, May 2013
*Fasting plasma glucose (FPG) measurements must be from 2 preceding days
72. Insulin NPH (Not truly basal) Glargine Detemir Degludec
Structure Crystalline suspension
of human insulin with
protamine and zinc
Addition of two
and substitution
of one amino
acid
Addition of
accylated fatty acid
chain at B
Deletion of B30, addition of
glutamic acid spacer and
diacylated fatty acid chain at
B29
Number of amino
acids
51 53 51 50
Carbon in side
chain
0 0 14 16
Mechanism of
protraction
Less solubility in the
extracellular fluid leads
to slower absorption
and a prolonged effect
Precipitation at
acidic pH
Binding to albumin Multihexamer chain formation
Terminal half life Variable 12.5 hrs 12.5 hrs 25.1-25.4 hrs
Duration of action 13-20 hrs Upto 24 hrs Upto 18-23 hrs Upto 42 hrs
Intra-patient
glycemic variability
High High Low Lowest
Exposure ratio: first
12 hrs to second 12
hrs after injection
60:40 50:50 50:50
Timing of
administration
Once or twice or thrice
daily
At the same time
everyday
Once or twice daily At any time, every day
Comparison of various basal insulins
73. Insulin NPH Glargine Detemir Degludec
Risk of hypoglycemia Present Low Low Least
Risk of nocturnal hypoglycemia Present Low Low Least
Risk of severe hypoglycemia Present Low Low Least
Injection site reactions Lesser than glargine Possible, because
of acidic pH
Rare Rare
Weight gain Yes Yes No Yes
Binding of IGF-1R (human
insulin 100)
641+51 18+2 2
Binding affinity to insulin
receptor (human insulin 100)
86+3 16+1 13-15
Use in renal impairment Dose needs to be adjusted Safe Safe Safe
Use in hepatic impairment Dose needs to be adjusted Safe Safe Safe
Miscibility with regular/rapid
acting insulin
Can be mixed with soluble
insulin without affecting
absorption kinetics of
either insulin
No No Yes
Miscibility with Glucagon like
peptide – 1 receptor agonists
Yes No Yes
Comparison of various basal insulins-2
74.
75. Clinical summary of Insulin Degludec
Successful non-inferior HbA1c reductions in type 1
or type 2 diabetes, based on treat-to-target trial
designs1-3
Significantly lower risk of nocturnal hypoglycemia
versus insulin glargine1–4
Flexibility in day-to-day dosing time when needed,
delivered in a once-daily dose4–7
17
1. Zinman et al. Diabetes Care 2012;35:2464–71; 2. Garber et al. Lancet 2012;379:1498–1507; 3. Heller. Lancet 2012;379:1489–97; 4.Keating. Drugs
2013;73:575–93; 5. Meneghini et al. Diabetes Care 2013;36:858–64; 6. Mathieu et al. J Clin Endocrinol Metab 2013;98:1154–62; 7. Tresiba® SmPC, Novo
Nordisk, May 2013