This document discusses glimepiride and its use in managing type 2 diabetes mellitus (T2DM). It begins with background on the global prevalence of diabetes and challenges in achieving glycemic control. It then focuses on glimepiride, explaining that it has a higher binding affinity and faster dissociation from sulfonylurea receptors compared to other sulfonylureas. This allows glimepiride to stimulate both the first and second phase of insulin secretion, improving fasting and postprandial hyperglycemia. In conclusion, glimepiride is an effective oral sulfonylurea option for the treatment of T2DM.
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
Diabetes mellitus (DM) is a significant public health problem associated with many debilitating health conditions
This presentation will briefly tackle management of Diabetes
Dipeptidyl peptidase inhibitors(DPP-IV): A deep insightRxVichuZ
This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
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
Diabetes mellitus (DM) is a significant public health problem associated with many debilitating health conditions
This presentation will briefly tackle management of Diabetes
Dipeptidyl peptidase inhibitors(DPP-IV): A deep insightRxVichuZ
This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
Sitagliptin an oral anti-diabetic agentAmruta Vaidya
A concise presentation on the DPP-IV inhibitor Sitagliptin an oral anti-diabetic agent. Its general mechanism of action, pharmacokinetics, safety is included.
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
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
Sitagliptin an oral anti-diabetic agentAmruta Vaidya
A concise presentation on the DPP-IV inhibitor Sitagliptin an oral anti-diabetic agent. Its general mechanism of action, pharmacokinetics, safety is included.
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
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
This is a 16 slide presentation covering the the classes of drugs used in T2DM and their molecular mechanisms of action. Provided by Professor John A Peters, University of Dundee.
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
Numbers to Remember, Important Numbers not to be missedUsama Ragab
Numbers to Remember, Important Numbers not to be missed
Normal blood glucose values
Fasting: < 100 mg/dL, fasting is defined as no caloric intake for at least 8 h.
2hPP: < 140 mg/dL
HbA1C: 5.7%
For Diagnosis of Prediabetes:
FPG 100 -125 mg/dL (IFG)
2-h PG during 75-g OGTT 140 - 199 mg/dL (IGT)
A1C 5.7–6.4%
Background
No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters.
Methods
Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured.
Results
The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin.
Conclusions
CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin
Fasting Ramadan carry many hazards to diabetic need to fast. Uncontrolled patients have a liability to some dangerous complications like DKA,HYPOGLYCEMIA,HHS AND thromboembolism
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
2. Estimated Global Prevalence Of Diabetes
2000 2014 2035
151 million 387 million 592 million
International Diabetes Federation. IDF Diabetes Atlas, 2014
3. Chan JCN, et al. Diabetes Care 2009;32:227-233.
3.6%
49.0%
64.4%
33.2%
19.2%
36.4%
Triglycerides <150 mg/dL
HDL cholesterol >40 mg/dL
LDL cholesterol <100 mg/dL
Blood Pressure <130/80 mmHg
HbA1c <7%
0% 20% 40% 60%
% Patients (with available
data)
Reached HbA1c,
blood pressure, and
LDL cholesterol
recommended
targets
Only 36% of T2D patients were at glycemic target
(HbA1c <7%) across regions
5. HbA1C(%)
UKPDS: Long-term follow-up
Bailey CJ & Day C. Br J Diabetes Vasc Dis 2008; 8:242–247.
Holman RR, et al. N Engl J Med 2008; 359:1577–1589.
Differences in mean glycated
hemoglobin levels between the
intensive therapy group and the
conventional-therapy group
were lost by 1 year, with similar
glycated hemoglobin
improvements thereafter in all
groups (p= not significant)
P=0.71
Glucose similar
BUT CV
events now
better
Metformin group 21% 33% 27%
6. A new paradigm
Del Prato S. Diabetologia 2009; 52:1219–1226.Del Prato S. Diabetologia 2009; 52:1219–1226.
7. Glycemic Goals
Parameter Normal
ADA
Goals
ACE/AACE
Goals
Fasting plasma glucose
(mg/dL)
< 100 90-130 < 110
Postprandial plasma glucose
(mg/dL)
< 120 < 180* < 140**
A1C (%) 4-6 < 7*** ≤ 6.5
*1-2 hours post-meal
**2 hours post-meal
***as close to normal as possible without undue risk of hypoglycemia
9. LIFESTYLE MEASURES
Then at each step, if not to target (generally HbA1c <7.0%)
IDF Treatment algorithm for people with type 2 diabetes
or
oror
Metformin
Sulfonylurea or
α-Glucosidase inhibitor
Sulfonylurea
α-Glucosidase inhibitor
or DPP-4 inhibitor
or Thiazolidinedione
Basal insulin or
Pre-mix insulin
GLP-1 agonist
Basal + meal-time insulin
Metformin
(if not first line)
α-Glucosidase inhibitor
or DPP-4 inhibitor
or Thiazolidinedione
Basal insulin or
Pre-mix insulin
(later basal + meal-time)
Alternative approachUsual approach
Consider
first line
Consider
second line
Consider
third line
Consider
fourth line
10.
11.
12. Management of Hyperglycemia in
Type 2 Diabetes, 2015:
A Patient-Centered Approach
Update to a PositionStatementof the AmericanDiabetesAssociation(ADA)
and the European Associationfor the Study of Diabetes(EASD)
Diabetes Care 2015;38:140–149
Diabetologia 2015;58:429–442
13. ANTI-HYPERGLYCEMIC THERAPY
• Glycemic targets
- HbA1c < 7.0% (mean PG 150-160mg/dl [8.3-8.9 mmol/l])
- Pre-prandial PG <130mg/dl (7.2 mmol/l)
- Post-prandial PG <180mg/dl (10.0mmol/l)
- Individualization is key:
Tighter targets (6.0 - 6.5%) - younger, healthier
Looser targets (7.5 - 8.0%+) - older, comorbidities,
hypoglycemia prone, etc.
- Avoidance of hypoglycemia
PG = plasma glucose
ADA-EASD Position Statement Update:
Management of Hyperglycemia in T2DM, 2015
Diabetes Care 2012;35:1364–1379; Diabetologia 2012;55:1577–1596
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
14. more
stringent
less
stringent
Patient attitude and
expected treatment efforts highly motivated, adherent,
excellent self-care capacities
less motivated, non-adherent,
poor self-care capacities
Risks potentially associated
with hypoglycemia and
other drug adverse effects
low high
Disease duration
newly diagnosed long-standing
Life expectancy
long short
Important comorbidities
absent severefew / mild
Established vascular
complications absent severefew / mild
Readily available limited
Usually not
modifiable
Potentially
modifiable
HbA1c
7%
PATIENT / DISEASE FEATURES
Approach to the management
of hyperglycemia
Resources and support
system
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Figure 1. Modulation of the
intensiveness of glucose
lowering therapy in T2DM
15. Healthy eating, weight control, increased physical activity & diabetes education
Metformin
high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
high
low risk
gain
edema, HF, fxs
low
Thiazolidine-
dione
intermediate
low risk
neutral
rare
high
DPP-4
inhibitor
highest
high risk
gain
hypoglycemia
variable
Insulin (basal)
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Basal Insulin +
Sulfonylurea
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
or
or
or
or
Thiazolidine-
dione
+
SU
DPP-4-i
GLP-1-RA
Insulin§
TZD
DPP-4-ior
or
or GLP-1-RA
high
low risk
loss
GI
high
GLP-1 receptor
agonist
Sulfonylurea
high
moderate risk
gain
hypoglycemia
low
SGLT2
inhibitor
intermediate
low risk
loss
GU, dehydration
high
SU
TZD
Insulin§
GLP-1 receptor
agonist
+
SGLT-2
Inhibitor
+
SU
TZD
Insulin§
Metformin
+
Metformin
+
or
or
or
or
SGLT2-i
or
or
or
SGLT2-i
Mono-
therapy
Efficacy*
Hypo risk
Weight
Side effects
Costs
Dual
therapy†
Efficacy*
Hypo risk
Weight
Side effects
Costs
Triple
therapy
or
or
DPP-4
Inhibitor
+
SU
TZD
Insulin§
SGLT2-i
or
or
or
SGLT2-i
or
DPP-4-i
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
injectable
therapy‡
GLP-1-RAMealtime Insulin
Insulin (basal)
+
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
HbA1c
≥9%
Metformin
intolerance or
contraindication
Uncontrolled
hyperglycemia
(catabolic features,
BG ≥300-350 mg/dl,
HbA1c ≥10-12%)
16. Oral Class Mechanism Advantages Disadvantages Cost
Biguanides • Ac vates AMP-
kinase (?other)
• ¯ Hepa c glucose
produc on
• Extensive experience
• No hypoglycemia
• Weight neutral
• ? ¯ CVD
• Gastrointes nal
• Lac c acidosis (rare)
• B-12 defici e ncy
• Contraindica ons
Low
Sulfonylureas • Closes KATP channels
• - Insulin secre on
• Extensive experience
• ¯ Microvascular risk
• Hypoglycemia
• - Weight
• Low durability
• ? Blunts ischemic
precondi oning
Low
Megli nides • Closes KATP channels
• - Insulin secre on
• ¯ Postprandial glucose
• Dosing flexibility
• Hypoglycemia
• - Weight
• ? Blunts ischemic
precondi oning
• Dosing frequency
Mod.
TZDs • PPAR-g ac vator
• - Insulin sensi vity
• No hypoglycemia
• Durability
• ¯ TGs (pio)
• - HDL-C
• - Weight
• Edema/heart failure
• Bone fractures
• - LDL-C (rosi)
Low
Extensive experience and efficacy for supporting
SU vs. new comers class
17. DPP-IV inhibitors and the debate of increase
the HF ?!
Death from CV causes, non-fatal MI or non-fatal stroke Death from CV causes, MI or ischemic stroke
18. Comparison :
Glimepiride vs DPP4 Inhibitors
*from Baseline in Premarketing trials
†2-6 mg Glimepiride vs Maximum DPP4 Inhibitors
‡Severe, Rare with both
#MI in UKPDS, ADOPT, ADVANCE,BARI trials[Diabetes Care,2015;38(1):166]
¶ Increased CHF [Clin Ther,2014;36(12):20729,CurrTreatOptionsCardiovascMed,2014;16(12):353]
Glimepiride DPP4 Inhibitors
Efficacy:∆A1c(minus) 25-30%* 8-12%*
Efficacy:∆A1c(minus) More or equal† Less or equal†
Cost Less More
Cost Efficacy More Less
Hypoglycemia ++++ ++
CVD Decreased# No Change¶
19. Injectabl
e
Class
Mechanism Advantages Disadvantages Cost
Amylin
mimetics
• Activates amylin
receptor
• glucagon
• gastric emptying
• satiety
• Weight
• Postprandial
glucose
• Gastrointestinal
• Modest A1c
• Injectable
• Hypo if insulin dose
not reduced
• Dosing frequency
• Training
requirements
High
GLP-1
receptor
agonists
• Activates GLP-1 R
• Insulin,
glucagon
• gastric emptying
• satiety
• Weight
• No hypoglycemia
• Postprandial
glucose
• Some CV risk
factors
• Gastrointestinal
• ? Pancreatitis
• Heart rate
• Medullary ca
(rodents)
• Injectable
• Training
requirements
High
Insulin • Activates insulin
receptor
• Myriad
• Universally effective
• Unlimited efficacy
• Microvascular risk
• Hypoglycemia
• Weight gain
• ? Mitogenicity
Variabl
e
Table 1. Properties of anti-hyperglycemic agents
Diabetes Care 2015;38:140-149;
Diabetologia 2015;58:429-442
21. Mechanism of action
Bind to the sulfonylurea receptor on the surface of the
β-cell
Closes KATP channels → Inhibit potassium efflux
(depolarizing the β-cells)
↑ Insulin secretion
23. K+
K+
GlimepirideGlibenclamide
Solubilisation
Glibenclamide Glimepiride
65 kDa
140 kDa
65 kDa
140 kDa
cell membrane
Sulfonylurea
receptor
Potassium channels
Glimepiride binds to the 65 kDa subunit of the sulfonylurea receptor;
glibenclamide binds to the 140 kDa subunit
Kramer W et al., Biochim Biophys Acta 1994;1191: 278-290
Hypothetical Model of Sulfonylurea Receptor in -cells
24. 0 10 20 30 40 50 60 70 80 90 minutes
3Hsulphonylureabound(%)
Glimepiride dissociates from its binding protein
8-9 times faster than glibenclamide
Glimepiride Glibenclamide
Müller G et al., Biochim Biophys Acta 1994;1191: 267-277.
80
60
40
20
100
1.5x106 RINm5F cells
were incubated
(4°C for 45 mins)
with 2 nM [3H]
Glimepiride or [3H]
glibenclamide. At
time zero,
dissociation was
induced by addition
of unlabeled
sulfonylurea (final
conc 2µM). Specific
binding is given as a
percentage of
specific binding at
time zero (100%).
Sulfonylurea Receptor Binding Affinity
Dissociation kinetics of 3H sulfonylurea binding to RINm5F cells
25. Acting on Both Phases of Insulin Secretion
Glimepiride: The only sulfonylurea to treat
fasting and postprandial hyperglycemia
First Phase Second Phase
Insulin secretion
Before treatment After Glimepiride treatment
Incrementalplasmainsulin
(pmol/L)
0
50
100
p=0.04
First and second phase insulin secretion
before and after treatment with Glimepiride
p=0.02
+Glimepiride
+Glimepiride
Korytkowski M et al. Diabetes Care 2002; 25(9):1607-11.
Euglycemic and
hyperglycemic
clamp studies in 11
obese patients with
T2DM with good
glycemic control
before and after 4
months treatment
with Glimepiride to
assess effect of
Glimepiride on insulin
secretion
26. Glimepiride Controls Glycemia with Less Insulin Secretion
For an equivalent glycemic effect, Glimepiride induces a
lower secretion of insulin
Mean variation of insulin and
glycemia over a 36-h period
Mean ratio between increased level
of insulin and reduced glycemia
5
10
15
0
1
2
3
Glimepiride Glibenclamide Gliclazide Glipizide
20
0
Glycemic
variation(%)
Insulinemia
(U/mL)
Glimepi
ride
Glibenclamide Glipizide Gliclazide
0.00
0.05
0.10
0.15
0.20
n=16
n=13
n=14
n=16
Ratio
Muller G, et al. Diabetes Res Clin Pract 1995; 28 (Suppl): S115-37
Sulfonylureas tested in
fasted male beagle
dogs to determine
ratios of mean plasma
insulin release/ blood
glucose decrease
27. Glimepiride reduces Insulin Resistance
Inukai K, et al. Diabetes Res Clin Pract 2005; 68: 250-257
0
1
2
3
4
5
HOMA-IR
6
6.5
7
7.5
8
HbA1c (%)
Baseline 6 months
Gliclazide or
glibenclamide
(n=52)
all patients BMI ≥ 25 BMI < 25
Glimepiride
(n=120)
all patients BMI ≥ 25 BMI < 25
Glimepiride
(n=120)
*
* *
Mean homeostasis model of insulin resistance (HOMA-IR) and
HbA1c (%) levels at baseline and after 6 months of treatment
*p< 0.05 vs baseline
Glimepiride maintains glycemic control and improves insulin sensitivity in
patients switching from gliclazide or glibenclamide
Gliclazide or
glibenclamide
(n=52)
Multicentre study in 172
Japanese patients in
whom glycemia was
inadequately controlled
(HbA1c ≥7%) by
gliclazide or
glibenclamide. Patients
were randomly assigned
to continue their usual
sulfonylurea or switch to
Glimepiride and were
followed for 6 months.
Baseline HbA1c: 7.5%
gliclazide/glibenclamide
; 7.6% Glimepiride
30. Glimepiride Efficacy Proven in Monotherapy
Tight glycemic control (HbA1c<7.2%) was
achieved in 69% of Glimepiride patients
and 32% of placebo patients
Schade DS et al. J Clin Pharmacol 1998;38:636-51
ΔinmedianHbA1c(%)
6.7%
Change from baseline to week 22
in median HbA1c
9.1%
7.9%
-1%
8.9%
Baseline HbA1c
-4
-3
-2
-1
0
HbA1c at Endpoint
-2.4%#
Glimepiride decreased FPG by 46 mg/dL
more and 2-hour PPG by 72 mg/dL more
than placebo (p<0.001)
Change from baseline to week 22 in
median FPG and 2-hour PPG
n=117 n=118 n=108 n=101
Δinglucoseconcentration(mg/dL)
FPG PPG
-59*
-117*
-13
-31
-140
-120
-100
-80
-60
-40
-20
0
Glimepiride Placebo
*p<0.001 vs placebo
Prospective,
randomized, double-
blind, placebo-
controlled, dose-
titration study. T2DM
patients received
Glimepiride (n=123) or
placebo (n=126) for a
10-week dose-titration
period and then the
optimal dose (1 to 8
mg) for 12 weeks. 54%
of patients on active
treatment received <4
mg/day Glimepiride
31. Modest efficacy of gliptins in meta-analyses1-3
1Amori et al. JAMA 2007;298:194-206.
2Richter et al. Cochrane Database Syst Rev 2008;Apr 16;(2):CD006739.
3Richter et al. Vasc Health Risk Manag 2008;4:753-68.
28994Gliptins vs. active control
419016Gliptins vs. placebo
30959Duration 12-24 wk vs. placebo
10957Duration 12 wk vs. placebo
17869Vildagliptin vs. placebo
24047Sitagliptin vs. placebo
No. of
patients
No. of
studies
-1.0 0 1.0
Favors gliptins Favors control
Weighted mean
difference, % (95% CI)
-0.74 (-0.85 to -0.62)
-0.70 (-0.83 to -0.58)
-0.78 (-1.00 to -0.56)
-0.73 (-0.94 to -0.52)
-0.74 (-0.84 to -0.63)
0.21 (0.02 to 0.39)
0.5-0.5-1.5
Weighted mean difference in change in HbA1C (%)
for gliptins vs. control in adults with type-2 diabetes1
32. A multicenter, 52-week, randomized, double-blind study in patients with type-2
diabetes inadequately controlled on metformin therapy
Vildagliptin, less effective than glimepiride?
1Ferranini et al. Diabetes Obes Metab 2009;11:157-66.
2Haute Autorité de Santé. 10 December 2008.
http://www.has-sante.fr/portail/upload/docs/application/pdf/2010-11/galvus_ct_5731.pdf.
100
0
36.5%
43.4%
Patients(%)
Target HbA1C ≤6.5%
at Week 522
50
Glimepiride
(n=1014)
Vildagliptin
(n=1043)
p=0.001
33. A multicenter, 30-week, randomized, double-blind study in patients with type-2
diabetes inadequately controlled on metformin therapy
Sitagliptin, less effective than glimepiride?
Goldstein et al. EASD 2010.
100
0
21.2%
27.5%
Patients(%)
Target HbA1C ≤6.5%
at Week 30
50
Glimepiride
(n=436)
Sitagliptin
(n=443)
Odds ratio (95% CI):
0.67 (0.47 to 0.95)
35. Reductions metabolic parameters after 12 months of
treatment with Glimepiride
Glimepiride Beneficial Effect on Cardiovascular Risk Factors
Glimepiride significantly reduces cardiovascular risk markers
De Rosa, et al. Clin Ther 2003; 25(2); 472-484
-45
-40
-35
-30
-25
-20
-15
-10
-5
0
Lp(a)
mg/dL
PAI-1
(ng/mL)
Hcy
(mol/L)
Changefrombaseline
-39.7*
mg/dL
-21.4†
ng/mL
-40.1*
mol/L
*p<0.01; †p<0.05 vs baseline
Lp(a) = Lipoprotein A
PAI-1 = plasminogen activator inhibitor-1
Hcy = homocysteine
Randomized, double-
blind study in which
patients with type 2
diabetes were treated
with Glimepiride
(n=62)or repaglinide
(n=62) for 12 months.
36. Glimepiride Beneficial Effect on Adiponectin Levels
Glimepiride increases plasma adiponectin levels
whilst achieving control of glycemia
Tsunekawa T, et al. Diabetes Care 2003; 26(2); 285-289
11
10
9
8
7
6
5
9
8
7
6
Baseline 4 weeks 8 weeks 12 weeks
Plasma adiponectin HbA1c (%)
Plasmaadiponectin
concentration(g/mL)
HbA1c(%)
8.4
8.2
6.5
7.5
6.96.6
10.2
Evolution of adiponectin and HbA1c levels during 12
weeks of Glimepiride treatment
A study in 17 elderly
patients with type 2
diabetes who were
treated with
Glimepiride for 12
weeks.
37. Change from baseline in lipid and lipoprotein
concentrations
Glimepiride Beneficial Effects on Lipid and
Lipoprotein Parameters
Glimepiride significantly improves lipid and lipoprotein parameters in
patients with metabolic syndrome vs rosiglitazone
Derosa G, et al. Diabetes Obes Metab 2006; 8: 197-205
TC LDL-C HDL-C TG Apo-AI Apo B
-60
-40
-20
0
20
* * *
*p<0.05 vs rosiglitazone + metformin
Glimepiride + metformin Rosiglitazone + metformin
Concentration(mg/dL)
Double-blind study
in which 95 patients
with metabolic
syndrome (T2DM,
triglycerides ≥150
mg/dL, BP ≥130/85
mmHg) were
randomized to
Glimepiride +
metformin or
rosiglitazone +
metformin for 12
months
38. Safety Profile of Glimepiride
Hypoglycemic Events
Impact on Weight
Cardiovascular Effects
39. Incidence of severe* hypoglycemic events
according to treatment
*Defined as requiring IV glucose or glucagon
Significantly lower incidence of severe hypoglycemic events with
Glimepiride vs glibenclamide (0.86 vs 5.6/1000 person-years)
Holstein A et al. Diabetes Met Res Rev 2001; 17:467-73
0.86
5.6
GlibenclamideGlimepiride
#Episodes/1000person-years
0
2
4
6
Prospective, population-
based, 4-year study to
compare frequency of
severe hypoglycemia in
patients with T2DM
treated with Glimepiride
(estimated n=1768)
versus glibenclamide
(estimated n=1721)
Safety: Hypoglycemia vs Glibenclamide
6.5x
less
risk of
hypo
40. Weitgasser R et al. Diabetes Res Clin Pract 2003; 61: 13-19
Mean intra-individual changes from baseline in body
weight and HbA1c
Months of treatment
Reduction in glycemia with Glimepiride is accompanied by
significant and stable weight loss
Changefrombaseline
*p<0.0001; †p<0.05; ‡p<0.005 vs baseline
4 12
- 1
- 2
- 3
18
0
Safety: Weight
-1.9*
-2.9†
-3.0‡
-1.4* -1.5*
-1.7*
Body weight (kg) HbA1c (%)
Open, uncontrolled,
observational study.
1770 T2DM patients
were enrolled and
284 were followed-up
for 1.5 years. Patients
received 0.5 to > 4
mg Glimepiride once
daily. Baseline HbA1c:
8.4%; body weight:
79.8kg
41. Safety: All-Cause Mortality
Retrospective,
observational cohort
study in T2D
outpatients. A total of
696 patients received
insulin secretagogues
in combination with
biguanides. A
Kaplan-Meier survival
analysis was
conducted in
patients treated with
metformin in
combination with
glibenclamide,
gliclazide,
repaglinide or
Glimepiride.
Monami M, et al. Diabetes Metab Res Rev 2006; 22(6): 477-482
Kaplan-Meier survival analysis
In combination with metformin, Glimepiride is associated with lower all-cause mortality
than other sulfonylureas with less selectivity for β-cell receptors
Glimepiride or gliclazide
Repaglinide
Glibenclamide
Time (months)
Cumulativesurvival
1.0
0.9
0.8
0.7
0.6
0 10.0 20.0 30.0 40.0
Glimepiride
Gliclazide
Repaglinide
Glibenclamide
Yearly mortality
0.4%
2.1%*
3.1%*
8.7%**
* P < 0.05 vs Glimepiride
**P <0.01 vs all comparators
43. Take Home Message
• DM is a complex disease with multiple etiologies.
• Glycemic control in important to reduce the risk of
microvascular complications of DM & glucose
control in the early years of DM may reduce the risk
of macrovascular disease.
• Various guidelines insists on the importance of
lifestyle modification & metformin as initial treatment
of T2DM.
• ADA-EASD 2015 position statement introduce the
concept of individualization of target & treatment of
DM.
• SU is a cornerstone in management of T2DM..
44. Glimepiride : Take Home Message
Unique dual mode of action
• Improves 1st and 2nd phases of insulin secretion
• Improves peripheral insulin resistance (extrapancreatic effects)
Fast and sustained blood glucose lowering effect in monotherapy
Suitable for combination with insulin and/or other oral antidiabetic
agents
Benefits beyond blood glucose-lowering
Suitable for use in all type 2 diabetes patients
Clinically proven safety profile
• Low incidence of hypoglycemic events
• No weight gain
• Lower risk of cardiovascular complications
Convenient, once-daily dosing resulting in excellent compliance