Glucagon Like Peptide-1 (GLP-1) Analogue
Liraglutide GLP-1 analogue with 97% homology to the human natural GLP.
Significance Better than natural GLP in Human body Longer half life periodHalf life period     Natural GLP-1 -> 1.5 minu...
Advantages Helps promoting weight loss Increase insulin secretion Will not cause hypoglycaemia Reduce glucagon secretion
Adverse Effects Mild   Nausea   Vomiting   Diarrhoea   Constipation
 Severe   -Pancreatitis   -Allergic reactions (Rashes, difficulty in breathing, tightness of chest, swelling of mouth, fa...
Critic Phase III LEAD studies LEAD- Liraglutide Effect and Action in Diabetes)LEAD 1 & 2         –       Add on therapyL...
Inclusion criteria Type 2 diabetic patients Age 18-80 years Under Oral Glucose lowering agents(OGLA) for the  past 3 mo...
Exclusion criteria Impaired renal or liver functions Proliferative retinopathy Usage of any other drugs apart from OGLA...
Outcome MeasuresPrimary outcome Measure     - HbA1CSecondary outcome Measures     - Fasting & Post Prandial Blood Glucose ...
LEAD 1 Combined Glimepride With      -Liraglutide      -Rosiglitazone &      -Placebo Studies are Double – blind, Double...
Outcome Measures HbA1C    -   -1.1% (Baseline 8.5%)                (p <0.001) Weight   -   -0.2 kg      (1.8 mg lirag.) ...
Critique Glimepride increases weight Liraglutide helps to decrease weight In combination......       -Only maximum dose...
Graph
LEAD 2 Combining Metformin with      - Liraglutide (Add-On Therapy)      - Glimepride      - Placebo Studies are Double ...
Outcome Measures HbA1C         -   -0.7 % (0.6 mg)                -   -1.0 % (1.2 & 1.8 mg) Body Weight   -   1.8 kg (0....
Blood pressure Systolic Blood pressure            - 2-3 mm Hg (1.2 & 1.8 mg lirag)            - 0.6 mm Hg (0.6 mg lirag) ...
LEAD 3 Compared-Liraglutide Vs Glimepride (Monotherapy)- a double-blind, double-dummy, active-  control, parallel-group s...
CritiqueAim: New treatments for type 2 diabetes mellitus are  needed to retain insulin–glucose coupling and  lower the ri...
Outcome Measures Primary outcomes  HbA1C          - 0.51%           (8mg Glimp)                 - 0.84 %          (1.2 mg...
Critique Symptoms of nausea was directly proportional to the weight loss
LEAD 4 Combined metformin and rosiglitazone with           - Liraglutide           - Placebo     (Triple therapy)
Outcome measures HbA1C         - 1.5%(Liraglutide)                - 0.5% (Placebo)          (Placebo+ Metformin+Rosiglita...
Critique 3 important factors in patho-physiology of elevated glucose level Insulin resistance Decrease in Beta-cell fun...
LEAD 4 Trial Claims that the triple therapy (metformin+ rosiglitazone + liraglutide) has the potential to promote weight...
LEAD 5 Metformin & Glimepiride withInsulin GlargineLiraglutidePlacebo            (Triple Therapy)
Outcome Measures HbA1C  Similar reduction         - 1.33% (liraglutide)         - 1.09 % (Insulin)But, Significant loss ...
LEAD 6 Compared  Liraglutide Vs Exenatide - a Double-blind, parallel group, multinational randomised control trial.
LiraglutideIn comparison with exenatide, Reduced HbA1C significantly (p<0.001) Reduced mean fasting glucose Lesser hypo...
 Therefore...This paper suggests the use of liraglutide over exenatide
Discussion Trial Design : Conducted in 600 centres in 40  countries. Lesser chances of bias Proves that research is rep...
 Aim:1. To address the issue that current drugs do not   control the diabetes in the long run and not able to   overcome ...
 Inclusion Criteria Exclusion Criteria Primary & Secondary outcome Measures HbA1c was measured using high-performance ...
Adverse events Only mild gastro intestinal symptoms were common Severe adverse event related to liraglutide like  PANCRE...
 But, Buse et al 2009 claims that as  obesity, hypertryglyceridemia and gallstones are risk  factors of pancreatitis whic...
Conclusion                    Though Liraglutide proves effective for a shorter period of 26 weeks. Its long term effects ...
Dr.V.Venugopal BNYS, FCR, M.Sc Diabetes          Yoga & Naturopathy Consultant                      Diabetes Specialist
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Liraglutide 1

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Liraglutide for Diabetes (type 2)- a crritical analysis

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Liraglutide 1

  1. 1. Glucagon Like Peptide-1 (GLP-1) Analogue
  2. 2. Liraglutide GLP-1 analogue with 97% homology to the human natural GLP.
  3. 3. Significance Better than natural GLP in Human body Longer half life periodHalf life period Natural GLP-1 -> 1.5 minutes Liraglutide -> 13 hours Therefore, can control blood glucose level for a longer period.
  4. 4. Advantages Helps promoting weight loss Increase insulin secretion Will not cause hypoglycaemia Reduce glucagon secretion
  5. 5. Adverse Effects Mild Nausea Vomiting Diarrhoea Constipation
  6. 6.  Severe -Pancreatitis -Allergic reactions (Rashes, difficulty in breathing, tightness of chest, swelling of mouth, face, lips or tongue) -Symptoms of thyroid Cancer (Lump or swelling in neck, trouble swallowing, hoarseness of voice)
  7. 7. Critic Phase III LEAD studies LEAD- Liraglutide Effect and Action in Diabetes)LEAD 1 & 2 – Add on therapyLEAD 3 - MonotherapyLEAD 4 & 5 - Triple TherapyLEAD 6 - Liraglutide Vs Exenatide (another GLP-1 analogue)
  8. 8. Inclusion criteria Type 2 diabetic patients Age 18-80 years Under Oral Glucose lowering agents(OGLA) for the past 3 months or more BMI <or= 45 kg/m2 and HbA1C 7-11%
  9. 9. Exclusion criteria Impaired renal or liver functions Proliferative retinopathy Usage of any other drugs apart from OGLA that could affect blood glucose levels Getting treated with systemic cortico-steroids Pregnant women (Animal studies have revealed evidence of foetal harm)
  10. 10. Outcome MeasuresPrimary outcome Measure - HbA1CSecondary outcome Measures - Fasting & Post Prandial Blood Glucose - Fasting Insulin and Glucagon Levels - Fasting C-peptide levels - Fasting pro insulin-insulin ratio - Body Weight - Blood pressure & - Lipid Profile
  11. 11. LEAD 1 Combined Glimepride With -Liraglutide -Rosiglitazone & -Placebo Studies are Double – blind, Double – dummy, Five – armed Parallel Randomised Controlled Trials .
  12. 12. Outcome Measures HbA1C - -1.1% (Baseline 8.5%) (p <0.001) Weight - -0.2 kg (1.8 mg lirag.) - +0.3kg (1.2 mg lirag.) - +0.7kg (0.6mg lirag.)
  13. 13. Critique Glimepride increases weight Liraglutide helps to decrease weight In combination...... -Only maximum dose of 1.8 mg liraglutide reduced body weight by 0.2kg - But, there was a increase in weight in other doses of 0.6 mg (+ 0.7kg) & 1.2 mg (+0.3kg)
  14. 14. Graph
  15. 15. LEAD 2 Combining Metformin with - Liraglutide (Add-On Therapy) - Glimepride - Placebo Studies are Double – blind, Double – dummy, Five – armed Parallel Randomised Controlled Trials
  16. 16. Outcome Measures HbA1C - -0.7 % (0.6 mg) - -1.0 % (1.2 & 1.8 mg) Body Weight - 1.8 kg (0.6 mg) - 2.6 kg (1.2 mg) - 2.8 kg (1.8 mg)
  17. 17. Blood pressure Systolic Blood pressure - 2-3 mm Hg (1.2 & 1.8 mg lirag) - 0.6 mm Hg (0.6 mg lirag) - 1.8 mm Hg (Placebo) - +0.4 mm Hg (Glimepride) Diastolic Blood pressure -Did not vary much from the baseline value(80mmHg)
  18. 18. LEAD 3 Compared-Liraglutide Vs Glimepride (Monotherapy)- a double-blind, double-dummy, active- control, parallel-group study trial
  19. 19. CritiqueAim: New treatments for type 2 diabetes mellitus are needed to retain insulin–glucose coupling and lower the risk of weight gain and hypoglycaemia...
  20. 20. Outcome Measures Primary outcomes HbA1C - 0.51% (8mg Glimp) - 0.84 % (1.2 mg lirag) - 1.14 % (1.8 mg lirag) - Not available (Placebo)
  21. 21. Critique Symptoms of nausea was directly proportional to the weight loss
  22. 22. LEAD 4 Combined metformin and rosiglitazone with - Liraglutide - Placebo (Triple therapy)
  23. 23. Outcome measures HbA1C - 1.5%(Liraglutide) - 0.5% (Placebo) (Placebo+ Metformin+Rosiglitazone)
  24. 24. Critique 3 important factors in patho-physiology of elevated glucose level Insulin resistance Decrease in Beta-cell function Increased production of glucose in liver (which is partially mediated by increased glucagon levels)
  25. 25. LEAD 4 Trial Claims that the triple therapy (metformin+ rosiglitazone + liraglutide) has the potential to promote weight loss (action of metformin and liraglutide) reduce insulin resistance (action of metformin and rosiglitazone) decreased production of glucagon (liraglutide)
  26. 26. LEAD 5 Metformin & Glimepiride withInsulin GlargineLiraglutidePlacebo (Triple Therapy)
  27. 27. Outcome Measures HbA1C Similar reduction - 1.33% (liraglutide) - 1.09 % (Insulin)But, Significant loss of body weight and systolic Blood pressure
  28. 28. LEAD 6 Compared Liraglutide Vs Exenatide - a Double-blind, parallel group, multinational randomised control trial.
  29. 29. LiraglutideIn comparison with exenatide, Reduced HbA1C significantly (p<0.001) Reduced mean fasting glucose Lesser hypoglycaemic episodes Nausea complaints were lesser Weight loss slightly better (3.24 kg liraglutide Vs. 2.87 kg in Exenatide)
  30. 30.  Therefore...This paper suggests the use of liraglutide over exenatide
  31. 31. Discussion Trial Design : Conducted in 600 centres in 40 countries. Lesser chances of bias Proves that research is repeatable Efficacy for a wider group of people, irrespective of ethnicity and country.
  32. 32.  Aim:1. To address the issue that current drugs do not control the diabetes in the long run and not able to overcome the decline of beta cell function2. To reduce the adverse effects of current Oral Glucose Lowering Agents(OGLA) [8] Clearly defined
  33. 33.  Inclusion Criteria Exclusion Criteria Primary & Secondary outcome Measures HbA1c was measured using high-performance liquid chromatography Statistics : ANCOVA – Analysis of Covariance Missing Data were imputed with Last Observation Carried Forward (LOCF)
  34. 34. Adverse events Only mild gastro intestinal symptoms were common Severe adverse event related to liraglutide like PANCREATITIS or others was rare - Only 3 out of the total 4456 participants got acute pancreatitis.
  35. 35.  But, Buse et al 2009 claims that as obesity, hypertryglyceridemia and gallstones are risk factors of pancreatitis which is also associated with diabetes mellitus. So, we cannot conclude that liraglutide as the cause of pancreatitis. It MIGHT be because of the progressive nature of diabetes.
  36. 36. Conclusion Though Liraglutide proves effective for a shorter period of 26 weeks. Its long term effects on blood glucose levels, complications of diabetes and the beta cell function has to be studied further.
  37. 37. Dr.V.Venugopal BNYS, FCR, M.Sc Diabetes Yoga & Naturopathy Consultant Diabetes Specialist

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