treatment of diabetes mellitus.pptx

Newer treatment for diabetes
Mellitus and latest protocol
Dr Indra Saini Guide
Dr Narendra Rawat Sir

• Diabetes mellitus is the group of common metabolic disorders that
share the phenotype of hyperglycemia.
• Depending upon the etiological factors contributing to hyperglycemia
include reduced insulin secretion, increase insulin resistance,
decrease glucose utilization, and increase glucose production.
• DM is the leading cause of end stage renal disease , increase risk of
cardiovascular mortality and morbidity.

Comprehensive medical care for diabetes
mellitus
• Glycemic goal and therapeutic plan
• Monitoring of blood glucose level –by SMBG and CGM
• HbA1c testing (2-4 time/year)
• Life style management
• Detection ,prevention and management of diabetes related complications
• Manage diabetes related condition-
hypertension
lipids
consider antiplatelet drugs

Life style Management in Diabetes care
• 1. Diabetes Self Management Education and Support (DSMES)- refer to way
to improve the patient knowledge, skills, abilities necessary for diabetes
self care and should also emphasizes on psychological issue and emotional
well being.
• 2. Nutrition therapy- Medical nutrition therapy (MNT)
• Used by ADA to describe the optimal coordination of calorie intake with
other therapy of diabetes (insulin, exercise, weight loss)
• MNT in type 1 DM - to minimize weight loss often due to insulin therapy
by placing limit on carbohydrate intake.
• IN type 2 DM MNT- focus on weight loss and address the greatly increase
prevalence of CV risk factor
• Emphasize on Modest calorie reduction ,increase physical activity and
weight loss

• 3. Physical activity-
• Patient with DM ADA recommends 150 min/week(distributed over at
least 3 day) of moderate aerobic physical activity with no gaps longer
than 2 days
• 4. Psychological care –
• Psychological assessment and support are critical part of
comprehensive diabetes care

Monitoring the level of glycemic control
• Short term glycemic control-
1. Self monitoring of blood glucose- the frequency of SMBG should be
individualized in type 1 and type 2 DM
2. Continuous glucose monitoring-
CGM technology utilise a sensor or electrode to detect interstitial
glucose which is equilibrium with blood glucose
• The sensor placed subcutaneously and replaced every 3-14 days
• CGM provide – TIME IN GLYCEMIC RANGE(TIR), ambulatory glucose
profile, amount of time in hypoglycaemic range and glucose
management indicator(GMI)

• CGM in type 1 DM decrease the frequency of hypoglycemia
• The combination of CGM and insulin infusion device now automate
insulin delivery with predictive suspension of insulin delivery to avoid
hypoglycemia.
• Long term glycemic control-measurement of HbA1c level that reflect
glycemic control over past 2-3 months
• The fructosamine assay measuring glycated albumin reflect the
glycemic status over the prior 2 week

Treatment of type 1 DM mellitus
In type 1 DM lack of endogenous insulin production, admiration of
basal insulin is essential for regulating glycogen breakdown ,
gluconeogenesis, lipolysis and ketogenesis
Intensive insulin therapy has the goal of achieving near normal
glycemia
Insulin regimen include-
1. Multiple component insulin regimen
2. Multiple daily injection (MDI)
3. Continuous subcutaneous insulin infusion (CSII)

Insulin preparations
TYPE ONSET
(Hr)
PEAK
(Hr)
DOA
(Hr)
Short acting
Ultra short acting
Regular insulin
Aspart
Glulisine
lispro
0.5-1
<0.25
<0.25
<0.25
2-4
0.5-1.5
4-8
3-5
Intermediate acting Isophane(NPH)
Lente
1-2 8-10 10-16
Long acting Glargine
Detemir
Degludec
2-4
1-4
1-9
-
20-24
12-24
42

Insulin degludec
• Ultra long acting insulin analogue, Threonine in B30 replaced by
Myristic acid
• It Self aggregation in subcutaneous tissue and bound to albumin in
circulation and prolong its duration of action .
Advantage -
• Hypoglycaemia less frequent than NPH
• Lesser Nocturnal hypoglycaemia
• Lesser or minimal weight gain
• Effective at physiological ph.

Insulin detemir
long acting basal insulin
• Bind to albumin and prolong its duration of action
• Onset 1-4 hr
• Duration of action 12-20 hr
• Twice daily injection required for 24 hr basal coverage

Insulin glargine
• Long acting analogue of human insulin
• Aspargine replaced by glycine at 21 in b chain
• Microscopic precipitate at physiological PH in subcutaneous tissue
• Duration of action 24 hr
• Peak less insulin
• Cannot be mixed with other insulin

Inhaled insulin
TYPES
• Afrezza –FDA approved in 2004
Rapid acting human insulin
• Similar to ultra short acting insulin ,should be used with long acting insulin
in type 1 DM
• Bioavailability- 9 to 22%
Contradiction-
• Smokers
• Poorly controlled lung disease- Asthma ,COPD
• Allergic patient

Newer Insulin delivery systems & glucose
monitors
• Insulin Pumps
• CSII ( continues subcutaneous insulin infusion)
• Dexcom G5 Mobile Continuous Glucose Monitoring System,
Approved December 20, 2016 [Sensor, transmitter, compatible
smart phone, or a smart watch]
• Freestyle Libre Flash Glucose Monitoring System, Approved
September 27, 2017 [sensor plus mobile reader]
• In Pen system (smart insulin pen]: FDA approved in 2017 for apple iOS
and for android version in 2018
• Is the first reusable insulin injector pen

Combination therapy in type 1 DM
• Add GLP-1 Receptor agonist along with basal insulin
• Potent glucose lowering action, less weight gain, hypoglycemia
• Two fixed dual combination products containing basal insulin and
GLP-1 RA are available
Insulin glargine with lixisenatide
Insulin degludec with liraglutide

INSUIN REGIMEN
• In all regimens long acting insulin supply basal insulin, where short acting
insulin supply prandial insulin injected just before ( <10 min )meal
• In general individual with type 1 DM require 0.3-0.7unit/kg per day
• Dived into 50% of daily insulin given as basal insulin and 50% as prandial
insulin
• CS II – very effective insulin regimen for the patient with type 1 DM
To the basal insulin infusion , a pre -prandial insulin ( bolus) is delivered
by insulin infusion device
• Hybrid closed loop system –recently become available that combine with
pre-prandial bolus and automated adjustment of insulin based on CGM

Newer drug approval
1.Tzield (teplizumab-mzwv) Injection
• Company: Provention Bio
• Date of Approval: November 17, 2022
• Tzield (teplizumab-mzwv) is a CD3-directed antibody
Treatment for: Delaying the Onset of Stage 3 Type 1Diabetes
2. Lyumjev (insulin lispro-aabc injection)
INDIANAPOLIS, June 15, 2020 /PRNewswire
- The U.S. Food and Drug Administration (FDA) has approved
Eli Lilly and Company's (NYSE: LLY)
Lyumjev (insulin lispro-aabc injection, 100 units/mL and 200 units/mL
New rapid-acting insulin indicated for type 1 diabetes and type 2 diabetes.
Contradiction- during episode of hypoglycaemia, hypersensitivity reaction

3.FDA Approves Semglee
• (insulin glargine-yfgn) as the First Interchangeable Biosimilar Insulin
Product for Treatment of Diabetes
Indicated to improve glycemic control in adults and pediatric patients
with Type 1 and Type 2 diabetes mellitus.
SILVER SPRING, Md., July 28, 2021 /PRNewswire/ -- Today,

Treatment for type 2 DM
1. Glycemic control –
• Life style/diet
• Exercise
• Medication
2. Treat associated condition-
• Dyslipidemia
• Hypertension, obesity
3. Management of complications

0ral Hypoglycemic Drug
DRUG MOA ADVANTAGE DISADVANTAGE CONTRAINDICATION
BIGUNAUIDES
metformin
Hepatic glucose
production
,increase insulin
sensitivity
Weight neutral,
no
hypoglycemia,
inexpensive
Diarrhoea,nausea
,lactic acidosis,
vitamin B12
deficiency
Renal
insufficiency(GFR<30
ml/min) hospitalized
patient, unstable
CHF, acidosis
SULFONYLUREA K +ATP channel
blocker, increase
insulin secretion
Lower post
prandial
glucose,
inexpensive
Hypoglycemia
,weight gain
Renal /liver
insufficiency
MEGLITINIDE Insulin secretion
increase
Faster onset,
lower post
prandial glucose
Hypoglycemia Renal /liver
insufficiency
ALPHA
GLUCOSIDASE
INHIBITOR
decrease GI
absorption of
glucose
Reduce post
prandial glucose
GI
flautuence,raise
liver enzyme
Renal /liver
insufficiency

,
THIAZOLIDINEDIONES Insulin resistance
Glucose utilization
increase
Lower insulin
requirement
Peripheral
edema,
CHF,weight
gain,fracture,
macular edema
CHF, Renal/liver insufficiency
DPP-4 INHIBITORS GLP-1 action
Insulin ,glucagon
No
hypoglycemia
Immune
mediated
dermatological
side effect
Reduced dose with renal
insufficiency

GLP-Receptor agonists
• Mechanism of action-
• Incretin effect- augment glucose dependent insulin secretion
suppression of glucagon
decrease gastric emptying
• Clincal efficacy- high to very high
no risk of hypoglycemia
weight loss
• Cardiorenal effect-
benefit effect on CVD
benefit effect on diabetic kidney disease

• Benefit on CVD include-
• dulaglutide, liraglutide, semaglutide
• Neutral effect on CVD- exenatide given once weekly
• lixisenatide
• Effect on DKD- dulaglutide, liraglutide,semaglutide
Shorter acting – daily injection required
Exenatide – twice daily injection required
no effect in CVD events
Liraglutide
Lixisenatide
longer acting- given weekly
Sustanied release exenatide
Dulaglutide
Semaglutide (oral)

• Adverse effect –
GI side effect- Nausea, vomiting ,diarrhea
increase risk of acute pancreatitis
• Contradiction – in patient with increase risk of medullary carcinoma
of thyroid

Glucose-dependent insulinotropic polypeptide
(GIP) receptor and GLP-1 receptor agonist
(tirzepatide)
Mechanism of action: GIP receptor and GLP-1 receptor agonist;
enhances first and second-phase insulin secretion, and reduces
glucagon levels, both in a glucose-dependent manner
• Clinical Efficacy profile: Very high glycemic efficacy;
• low inherent risk of hypoglycaemia;
• weight loss (high);
• Cardiorenal effects unknown (trials in progress)

DPP-4 INHIBITOR
• Mechanism of action- increase the effect of incretin by inhibiting DPP-
4 ENZYME
• Intermediate glucose-lowering efficacy
• Neutral effect on weight, generally well tolerated
• Minimal risk of hypoglycemia
• RENAL Adjustment required- sitagliptin, sexagliptin, alogliptin
• No dose adjustment required for linagliptin
• Usually neutral effect in CVD, HF,DKD

Mechanism of action: Reduce renal tubular glucose reabsorption
glucose lowering effect independent of Insulin
they reduce the reabsorbtion of Na so mild diuretic effect
and reduction of SBP
• Clinical Efficacy Profile: Intermediate to high glucose-lowering efficacy
lower at lower eGFR;
NO risk of hypoglycemia;
Intermediate weight loss
• Cardiorenal Effects: Demonstrated protective effects in studied trial populations:
• Reduction in major adverse cardiovascular events
• Reduction in overall CV death (with heterogeneity across the class)
• Reduction in risk of hospitalisation for heart failure
• Reduction in risk of kidney outcomes
SGLT2 Inhibitors

• Effect on CVD , HF, DKD – all SGLT -2 inhibitors reduced hospitalization
for HF, reduce progression of diabetic kidney disease
• Canagliflozin
• Empagliflozin
• Dafagliflozin
• glucose lowering effect is lower if eGFR lower ( eGFR<45 /min)
• Disadvantage –
• Increase risk of UTI, ketoacidosis in DM 1
• Contradiction – type 1 and pancreatic form of diabetes

N Engl J Med 2019; 381:1995-2008
Patient Population: With heart failure and a reduced ejection fraction, regardless of the
presence or absence of diabetes.
n = 4744
Dose: Dapagliflozin 10 mg daily
*≥400 pg/ml if HF hospitalization within ≤12 months; ≥900 pg/ml if atrial fibrillation/flutter
30
The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial
(DAPA-HF)

N Engl J Med 2019; 381:1995-2008
The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF)
-26% -30%
-18% -17%
The primary composite outcome
of CV death & hospitalization for
heart failure reduced by 26%.
• First episode of worsening HF was
reduced by 30%
• The risk of CV death was reduced by
18%
In patients with HF with reduced Ejection Fraction, the risk of
worsening HF or death from CV causes was lower among those
who received Dapagliflozin than among those who received
placebo, regardless of the presence or absence of diabetes
31

Empagliflozin Causes Regression of Albuminuria in Patients with
Prior Micro- or Macro-albuminuria (EMPA-REG OUTCOME)
Patients with Prior Microalbuminuria
Regression to Normoalbuminuria
Patients with Prior Macroalbuminuria
Regression to Normo / Microalbuminuria
43% ↑ Likelihood
with Empagliflozin
82% ↑ Likelihood
with Empagliflozin
Cherney DZI et al. Lancet Diabetes Endocrinol. 2017 Aug;5(8):610-21.
UACR: Urine Albumin-Creatinine Ratio. Normoalbuminuria: UACR <30 mg/g. Microalbuminuria: UACR ≥30 to ≤300 mg/g. Macroalbuminuria: UACR >300 mg/g.

Guideline Recommendations
In patients with type 2 diabetes
who have established
atherosclerotic cardiovascular
disease or indicators of high risk,
established kidney disease, or heart failure
ADA Recommends
Early Combination Therapy with SGLT2i & DPP4i is
recommended as part of the glucose-lowering
regimen independent of A1C and in consideration
of patient-specific factors .1
1. Diabetes Care Volume 44, Supplement 1, January 2021
33

Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB
Diabetes Care 2022; https://doi.org/10.2337/dci22-0034. Diabetologia 2022; https://doi.org/10.1007/s00125-022-05787-2.

Choosing glucose-lowering medication in people with
CVD
ASCVD = atherosclerotic cardiovascular disease
Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova
T, Tsapas A, Buse JB
•In people with established CVD, a GLP-1RA with proven
benefit should be used to reduce MACE or an SGLT2i with
proven benefit should be used to reduce MACE and HF and
improve kidney outcomes.

chronic kidney disease
•In people with CKD, SGLT-2 inhibitors and GLP-1RA reduce
risk of MACE independent of eGFR.
•In people with CKD, SGLT2i also reduce risks of HF and kidney
outcomes (including end-stage kidney disease

heart failure
In people with heart failure SGLT2i should be used because they improve
heart failure and kidney outcomes.

Insulin therapy in type 2 DM
Insulin therapy indicated in patient with –
• Lean individual or with severe weight loss
• Underlying renal and hepatic disease
• Acute severe hyperglycemia
• If Hba1c% >9%
• Initiate with single dose of long acting insulin (0.1-0.4U /kg)per day at
bed time may be adjusted in 10-20% increment as detected by SMBG
result.

ADA Standards of Care - 2022 Guidance

Other therapy for diabetes mellitus
• Metabolic –
• bariatric surgery- should be considered in individual in BMI>30Kg/m2
if hyperglycemia inadequately controlled despite optimal medical
therapy
• Short term caloric restriction-(very low calorie diet, typically (800-
1000 calorie/day)
• Pancreatic transplantation –whole pancreases or pancreatic islet
transplantation indicated in patient with severe metabolic instability
or patient already require immunosuppression for kidney or other
organ transplantation.

Bile Acid-Binding Resins
• Colesvelam:
• Approved for the treatment of type 2 diabetes..
• Mechanism of Action.
• Bile acid metabolism is abnormal in patients with type 2 diabetes , act as signaling
molecules through nuclear receptors, some of which may act as glucose sensors.
• Adverse effect :
• dyspepsia, abdominal pain, and nausea affecting up to 10% of treated patients.
increase plasma triglycerides
Pregnancy category B drug
Therapeutic Uses. Treatment of hypercholesterolemia and may be used for treatment of
type 2 diabetes

Emerging therapies
• 1.Activator of glucokinase
• Glucokinase is an enzyme present in pancreases alpha and beta cell
• Glukinase activation act as prominent regulator of hepatic intermediary and
energy metabolic pathway
• Trial of two drugs MK0941 and piragliptin were terminated previously.
• Inhibitor of 11 beta hydroxysteroid dehydrogenase
• GPR-40 agonists
• targeting glucose dependent insulinotropic polypeptide receptor and GLP-1
receptor. A novel GPR40 agonist TAK-875 shown to significantly improvement in
glycemic control.
• Combined SGLT-1 AND SGLT-2 Inhibitors
• Anti CD-3 monoclonal antibody-otelixizumab,teplizumuab

Imeglimin (twymeeg)-
• Oral antidiabetic
• Approved in Japan in 2021
• Mode of action –
1.direct effect on islet –beta cell to enhance glucose stimulated insulin
secretion (GSIS)
• Prevent loss of beta cell mass
2. Enhance insulin action in both liver skeletal muscle
Use – type 2 DM as an Add on therapy with metformin or sitagliptin

treatment of diabetes mellitus.pptx

Recommended

Recommended

More Related Content

Similar to treatment of diabetes mellitus.pptx

Similar to treatment of diabetes mellitus.pptx (20)

More from Roop

More from Roop (12)

Recently uploaded

Recently uploaded (20)

treatment of diabetes mellitus.pptx