oral antidiabetics by dr. mushtaq ahmed, associate professor, pharmacology, pims punjab
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DR. MUSHTAQ AHMEDDR. MUSHTAQ AHMEDAssociate Professor, PharmacologyAssociate Professor, Pharmacology
Punjab Institute of Medical Sciences, Jalandhar, Punjab Institute of Medical Sciences, Jalandhar, INDIAINDIA
Diabetes MellitusDiabetes Mellitus
Diabetes mellitus (DM) is a metabolic disorder resulting from a Diabetes mellitus (DM) is a metabolic disorder resulting from a
defect in insulin secretion or insulin action, or bothdefect in insulin secretion or insulin action, or both Classification of DM Type 1
• Immune Mediated• Idiopathic
Type 2 (Maturity onset)
Other specific types
Gestational Diabetes mellitus
Prevalence of DM Prevalence of DM
IndiaIndia is the is the “Diabetes Capital”“Diabetes Capital” of the World of the World
In 2010 - >200 million people worldwide had DM and 300 In 2010 - >200 million people worldwide had DM and 300 million will subsequently have the disease by 2025million will subsequently have the disease by 2025
India had 32 million diabetic subjects in the year 2000 India had 32 million diabetic subjects in the year 2000 and this number would increase to 80 million by the year and this number would increase to 80 million by the year 20302030
There is increased incidence of DM in urban population There is increased incidence of DM in urban population than rural than rural
ClassificationClassification
Type 1Type 1 Immune MediatedImmune Mediated IdiopathicIdiopathic
Type 2 (Maturity onset)Type 2 (Maturity onset)
Other specific typesOther specific types
Gestational Diabetes Gestational Diabetes mellitusmellitus
Development and Progression of Type 2 Diabetes*Development and Progression of Type 2 Diabetes*
Progression of Disease
Impaired Glucose Tolerance Impaired Glucose Tolerance
Insulin level
Insulin resistance
Hepatic glucose production
Diabetes DiagnosisDiabetes Diagnosis
Postprandial glucose
Fasting glucose
β-cell function
Frank DiabetesFrank Diabetes
4–7 years
0
50
100
Rel
ativ
e %
Insulinresistance
Genetic susceptibility,obesity, Western lifestyle
Type 2 diabetes
IR-celldysfunction
Pathophysiologic Defects in Type 2 Diabetes
- cell - cell DysfunctionDysfunction
Chronic hyperglycaemia
Oversecretion of insulin to compensate for insulin resistance
High circulating free fatty acids
Glucotoxicity
Pancreas
Lipotoxicity
- cell dysfunction
Insulin resistance – reduced response to circulating insulinInsulin resistance – reduced response to circulating insulin
Insulinresistance
Glucose output
Glucose uptake Glucose uptake
HyperglycaemiaHyperglycaemia
Liver Muscle Adiposetissue
IR
Insulin Resistance
Causes of Insulin ResistanceCauses of Insulin Resistance
Defect (structural) in insulin molecule
Elevated levels of insulin antagonists (counter-regulatory hormones)
Target tissue defects (Major cause)
Sites of action of Antidiabetics
What is the role of an ideal oral hypoglycaemic agent? What is the role of an ideal oral hypoglycaemic agent?
Conserve islet cell function - delay the subsequent Conserve islet cell function - delay the subsequent use of insulin.use of insulin.
Improve patient compliance- single daily dosing.Improve patient compliance- single daily dosing.
Reduce the incidence of hypoglycaemic eventsReduce the incidence of hypoglycaemic events
Management of DiabetesManagement of Diabetes
Role of Exercise in Type 2 DMRole of Exercise in Type 2 DM
• Exercise - probably the best treatment for Exercise - probably the best treatment for type 2 diabetestype 2 diabetes
• Lowers blood sugarLowers blood sugar
• Decrease insulin resistanceDecrease insulin resistance
• Raise metabolismRaise metabolism
• Improve blood flow through capillariesImprove blood flow through capillaries
• Improve stroke volume & blood lipidsImprove stroke volume & blood lipids
• Control & prevent moderate hypertensionControl & prevent moderate hypertension
• Decrease body massDecrease body mass
Pancreas – the site of actionPancreas – the site of action
Stimulate insulin secretion• Sulfonylurea• Meglitinide
Pancrease
Classification of Oral AntidiabeticsClassification of Oral Antidiabetics
Oral Hypoglycaemic AgentsOral Hypoglycaemic Agents 1. 1. SulphonylureasSulphonylureas
First Generation: First Generation: Tolbutamide, Chlorpropamide Tolbutamide, Chlorpropamide Second Generation: Second Generation: Glibenclamide (glyburide), Glipizide, Glibenclamide (glyburide), Glipizide,
Gliclazide, Glimepiride Gliclazide, Glimepiride
2. 2. Meglitinide AnaloguesMeglitinide Analogues: : Repaglinide, NateglinideRepaglinide, Nateglinide
Oral Hypoglycaemic AgentsOral Hypoglycaemic Agents
SulphonylureasSulphonylureas
First GenerationFirst Generation
TolbutamideTolbutamide
• O.O.A. is within one hour & lasts for 6-12 HrsO.O.A. is within one hour & lasts for 6-12 Hrs
• It is weaker, short acting, less likely to cause hypoglycemiaIt is weaker, short acting, less likely to cause hypoglycemia
Chlorpropamide Chlorpropamide
• O.O.A. is within one hour & lasts for 24-60 HrsO.O.A. is within one hour & lasts for 24-60 Hrs
• It is more potent, long lasting, risk of prolonged hypoglycemiaIt is more potent, long lasting, risk of prolonged hypoglycemia
• Potentiates ADH actionPotentiates ADH action
Sulphonylureas (contd)Sulphonylureas (contd)
Second Generation Second Generation Glibenclamide (glyburide)Glibenclamide (glyburide)• O.O.A. is within 1-4 hours & lasts for 10-24 HrsO.O.A. is within 1-4 hours & lasts for 10-24 Hrs
• It is more potent than tolbutamide, risk of severe hypo.It is more potent than tolbutamide, risk of severe hypo.
GlipizideGlipizide• O.O.A. is within 1-3 hours & lasts for 10-24 HrsO.O.A. is within 1-3 hours & lasts for 10-24 Hrs
• Less potent than glibenclamide but more potent than tolbutamideLess potent than glibenclamide but more potent than tolbutamide
• Risk of prolonged hypoglycemiaRisk of prolonged hypoglycemia
GliclazideGliclazide• O.O.A. & D.O.A, same as glipizideO.O.A. & D.O.A, same as glipizide
• More potent than tolbutamideMore potent than tolbutamide
• Has an antioxdent and antiplatelet actionHas an antioxdent and antiplatelet action
• Less weight gain Less weight gain
Glimepiride: Glimepiride:
• Same as glipizideSame as glipizide
Sulphonylureas Sulphonylureas M.O.AM.O.A• Stimulates Insulin release Stimulates Insulin release from from β- β- cellscells
• Inhibits SUR-1 receptors present on ATP sensitive KInhibits SUR-1 receptors present on ATP sensitive K++ channels → depolarization channels → depolarization followed by Cafollowed by Ca++ entry → insulin release entry → insulin release
• Glucagon levels are suppressedGlucagon levels are suppressed
PharmacokineticsPharmacokinetics• well absorbedwell absorbed
• PPB is highPPB is high
• Metabolized in liver or kidney and excreted in urineMetabolized in liver or kidney and excreted in urine
Adverse effectsAdverse effects• HypoglycemiaHypoglycemia
• Weight gainWeight gain• Cross placental barrier – fetal hypoglycemiaCross placental barrier – fetal hypoglycemia (avoid in gestational DM)(avoid in gestational DM)
Contra indicationsContra indications• Ketocanazole, chloramphenicol and anticoagulants- inhibit their metabolismKetocanazole, chloramphenicol and anticoagulants- inhibit their metabolism
• Sulfonamides, salicylates etc- protein binding displacementSulfonamides, salicylates etc- protein binding displacement
• Propranolol masks the symptoms of sulfonylureasPropranolol masks the symptoms of sulfonylureas
Meglitinide AnaloguesMeglitinide Analogues
RepaglinideRepaglinide• Its O.O.A is within one hour & lasts for 4-5 hrsIts O.O.A is within one hour & lasts for 4-5 hrs• Dose 0.25-4mg before each mealDose 0.25-4mg before each meal
NateglinideNateglinide• Its O.O.A & D.O.A, same as repaglinideIts O.O.A & D.O.A, same as repaglinide• Dose 60-120mg before each mealDose 60-120mg before each meal• Hypoglycemic risk is lowHypoglycemic risk is low
M.A.O M.A.O • Stimulate insulin releaseStimulate insulin release, same as sulfonylurea, same as sulfonylurea• Administered before meal to control PP blood glucoseAdministered before meal to control PP blood glucose
Advantages of Nateglinide/RepaglinideAdvantages of Nateglinide/Repaglinide
Flexibility in mealtime dosing - ‘Ramzan Drug’Flexibility in mealtime dosing - ‘Ramzan Drug’
No significant increase in bodyweightNo significant increase in bodyweight
Can be utillised in mild to moderate renal failureCan be utillised in mild to moderate renal failure
Nateglinide: approved in hepatic failure Nateglinide: approved in hepatic failure
Dosage:Dosage:
Repaglinide: Repaglinide: 0.5mg/1mg/2mg/4mg per dose per meal0.5mg/1mg/2mg/4mg per dose per meal
Nateglinide: Nateglinide: 60mg/120mg per dose per meal60mg/120mg per dose per meal
Lower incidence of hypoglycemiaLower incidence of hypoglycemia
Useful SituationsUseful Situations
– Elderly patients in whom hypoglycaemia is a concern Elderly patients in whom hypoglycaemia is a concern
– Patients with kidney failure or mild hepatic impairmentPatients with kidney failure or mild hepatic impairment
– patients taking low-dose sulphonylureas who encounter patients taking low-dose sulphonylureas who encounter problems with hypoglycaemiaproblems with hypoglycaemia
– Patients with irregular meal patternsPatients with irregular meal patterns
Int J Clin Pract. 2003 Jul-Aug;57(6):535-41.
Summary of insulin release and MOA of AntidiabeticsSummary of insulin release and MOA of Antidiabetics
ATP Dependent KATP Dependent K+ + ChannelChannel
Insulin actions at the target cellsInsulin actions at the target cells
Sites of action of Antihyperglycemic AgentsSites of action of Antihyperglycemic Agents
Liver Muscle Adiposetissue
• Bigunides - Metformin• Thiazolidonediones – Rosiglitazone etc.
UUPPTTAAKKEE
UTILIZATION Of GLUCOSEUTILIZATION Of GLUCOSE
Antihyperglycemic AgentsAntihyperglycemic Agents
BiguanidesBiguanides MetforminMetformin
The primary drug of choice for diabetes by ADA guidelines. The primary drug of choice for diabetes by ADA guidelines.
• Does not stimulate insulin releaseDoes not stimulate insulin release
• Not dependent on functional Not dependent on functional β- β- cells for its actioncells for its action
• Does not lower blood glucose in normal subjectsDoes not lower blood glucose in normal subjects
• Causes anorexia, no weight gainCauses anorexia, no weight gain
• As monotherapy, rarely causes hypoglycemiaAs monotherapy, rarely causes hypoglycemia
Dose:Dose:
500mg twice a day after meals 500mg twice a day after meals
Biguanides ContdBiguanides Contd
Advantages:Advantages: Perpetuates weight lossPerpetuates weight loss Can be combined with insulin to reduce Can be combined with insulin to reduce
insulin requirementsinsulin requirements Decreases risk of macro & Decreases risk of macro &
microvascular microvascular diseasediseaseDisadvantages:Disadvantages:
Nausea, Vomiting and diarhorrea (5%), Nausea, Vomiting and diarhorrea (5%), Vitamin B12 Deficiency (0.5%) Vitamin B12 Deficiency (0.5%)
Adverse effect:Adverse effect: Nausea, metallic taste, anorexia,Nausea, metallic taste, anorexia, flatulence & diarrhoea flatulence & diarrhoea Non diabetic use of Metformin:Non diabetic use of Metformin: Hirsutism with PCOD to enhance Hirsutism with PCOD to enhance fertility in women fertility in women
PhenforminPhenformin • Its Its use has been discontinueduse has been discontinued because of because of
lacticacidosislacticacidosis
Biguanides ContdBiguanides Contd
Biguanides ContdBiguanides Contd
M.O.AM.O.A• Increased uptake and utilization of glucose by muscles → Increased uptake and utilization of glucose by muscles →
reduce insulin resistancereduce insulin resistance• Inhibition of hepatic and renal gluconeogenesis → reduce Inhibition of hepatic and renal gluconeogenesis → reduce
hepatic glucose outputhepatic glucose output• Slowing of glucose absorption from GITSlowing of glucose absorption from GIT• Promotion of insulin binding to its receptorPromotion of insulin binding to its receptor
PK PK • No PPB, Plasma tNo PPB, Plasma t1/21/2 2-3 hours 2-3 hours• Excreted unchanged by kidneysExcreted unchanged by kidneys
Thiazolidinediones (Glitazones)Thiazolidinediones (Glitazones) New class of drugs – acts as agonist to nuclear New class of drugs – acts as agonist to nuclear
receptor PPAR-receptor PPAR-Ƴ in adipose tissue, sk. Muscle Ƴ in adipose tissue, sk. Muscle and liver.and liver.
Pioglitazone Pioglitazone • D.O.A. more than 24hrsD.O.A. more than 24hrs• 10-45 mg OD10-45 mg OD
Rosiglitazone Rosiglitazone (withdrawn from the market in Oct. 2010 b/o risk of (withdrawn from the market in Oct. 2010 b/o risk of Heart failure and MI) Heart failure and MI)
• D.O.A. same as pioglitazoneD.O.A. same as pioglitazone• Dose 4-8mg ODDose 4-8mg OD
Glitazones ContdGlitazones Contd
MOAMOA• Stimulates (nuclear receptor) i.e. Stimulates (nuclear receptor) i.e. PPeroxisome eroxisome PProliferator roliferator AActivated ctivated
RReceptor-gamma (eceptor-gamma (PPAR-ƳPPAR-Ƴ) → promotes transcription of insulin ) → promotes transcription of insulin responsive genes which control glucose & lipid metabolism → responsive genes which control glucose & lipid metabolism → ↑ ↑ insulin sensitivityinsulin sensitivity & & ↓ insulin resistance↓ insulin resistance
• Promotes uptake and utilization of glucose by increasing the GLUT-4 Promotes uptake and utilization of glucose by increasing the GLUT-4 transpotorstranspotors
• Decrease glucose output by inhibiting gluconeogenesisDecrease glucose output by inhibiting gluconeogenesis
AEAE• Weight gain. hepatotoxicity is rare, yet LFT are advisableWeight gain. hepatotoxicity is rare, yet LFT are advisable
CICI• Hepatic failure, pregnancy, lactating mother, children and heart failureHepatic failure, pregnancy, lactating mother, children and heart failure
GIT As a Site of TargetGIT As a Site of Target
Alpha glucosidase enzyme
facilitates digestion of complex
starches, oligosaccharides and
disaccharides into
monosaccharides so that these
are absorbed from the small
intestine. The digestion is also
facilitated by pancreatic alpha
amylase.
αα-Glycosidase Inhibitors-Glycosidase Inhibitors
Acarbose, Miglitol, VogliboseAcarbose, Miglitol, Voglibose
Work on the brush border of the intestine cause Work on the brush border of the intestine cause carbohydrate malabsorptioncarbohydrate malabsorption
• Reduce post meal hyperglycemiaReduce post meal hyperglycemia• Regular use tend to lower HbARegular use tend to lower HbA1c1c, triglycerides , triglycerides
and body weightand body weight• Do not directly affect insulin secretionDo not directly affect insulin secretion• No hypoglycemiaNo hypoglycemia• Dose:Dose: 50-100mg TDS 50-100mg TDS
αα-Glycosidase Inhibitors contd.-Glycosidase Inhibitors contd.
M.O.AM.O.A• Reduce PP digestion and absorption of Reduce PP digestion and absorption of
carbohydrates by inhibiting carbohydrates by inhibiting αα – glucosidase – glucosidase enzymeenzyme
PK PK • Absorption of acarbose is minimal, but Absorption of acarbose is minimal, but
miglitol miglitol is absorbed wellis absorbed well• A Part of acarbose is excreted unchanged A Part of acarbose is excreted unchanged
while a part is metabolized by intestinal while a part is metabolized by intestinal bacterial flora bacterial flora
αα-Glycosidase Inhibitors Contd.-Glycosidase Inhibitors Contd.
Advantages: Advantages: • Selective for postprandial hyperglycaemiaSelective for postprandial hyperglycaemia• No hypoglycaemic symptoms No hypoglycaemic symptoms
Disadvantages:Disadvantages:• Abdominal distension and flatusAbdominal distension and flatus• Only effective in mild hyperglycaemiaOnly effective in mild hyperglycaemia
Dose:Dose: Acarbose - 25 mg to 50mg TIDAcarbose - 25 mg to 50mg TID Miglitol - 25mg to 100mg TIDMiglitol - 25mg to 100mg TID Voglibose - 0.2 to 0.3 mg TIDVoglibose - 0.2 to 0.3 mg TID
What are Incretins?What are Incretins?
I s a group of hormones (GLP & GIP) – released after meals and augment glucose-dependent insulin secretion
GLP-1 (glucagon-like peptide 1) (*More Imp)
• is a prominent insulinotrophic incretin.• half life- 1-2 min.• metabolized quickly by DPPIV enzyme.
GIP: Glucose-dependent insulinotrophic polypeptide
Small effect in Type 2 diabetes.
Incretin conceptIncretin concept
Insulin secretion dynamics is dependent on the Insulin secretion dynamics is dependent on the method of administration of glucosemethod of administration of glucose
Intravenous glucose gives a marked first and Intravenous glucose gives a marked first and second phase responsesecond phase response
Oral glucose gives less marked first and second Oral glucose gives less marked first and second phase insulin response, but a prolonged and phase insulin response, but a prolonged and higher insulin concentrationhigher insulin concentration
Insu
lin c
once
ntra
tion
0 10 20 30 40 50 60 70 80 90
Minutes
Glucose given orally
Glucose given intravenously
Insulin secretion profilesInsulin secretion profiles
Insu
lin c
once
ntra
tion
0 10 20 30 40 50 60 70 80 90
Minutes
Glucose given orally
Glucose given intravenously to achieve the same profile
Incretin effect
Iso - glycemic profilesIso - glycemic profiles
20001960
‘Enteroinsular axis’ named
Incretin defined
Discovered as proglucagon gene product
Receptor cloned
1930 19801970 1990
Normalisation of BG in type
2 diabetes
Insulinotropic action of incretins
confirmed
Incretin and enteroinsular axis further
defined
History of GLP-1History of GLP-1
GLP-1 localisationGLP-1 localisation
Cleaved from proglucagon in Cleaved from proglucagon in intestinal L-cells (and neurons in intestinal L-cells (and neurons in hindbrain/hypothalamus)hindbrain/hypothalamus)
Secreted in response to meal Secreted in response to meal ingestioningestion
Cleared via the kidneysCleared via the kidneys
Incretin-MimeticsIncretin-Mimetics Incretin–mimeticsIncretin–mimetics• GGlucagon lucagon LLike ike PPeptide – eptide – 11 ( (GLP-1GLP-1) → released after meals from the upper & ) → released after meals from the upper &
lower bowel → augment glucose dependent insulin secretion, during the phase lower bowel → augment glucose dependent insulin secretion, during the phase of nutrition absorption from GITof nutrition absorption from GIT
• t ½ GLP-1 – 1 to 2 mint ½ GLP-1 – 1 to 2 min
• Metabolized quickly by Metabolized quickly by DPP-IV enzymeDPP-IV enzyme
Exenatide [incretin Exenatide [incretin (GLP-1) (GLP-1) agonist] agonist] • Obtained from salivary gland venom of Gila monsterObtained from salivary gland venom of Gila monster
• Resistant to DPP-IV degradationResistant to DPP-IV degradation
• Potent agonist of GLP-1 receptor, Orally inactivePotent agonist of GLP-1 receptor, Orally inactive
• Given SCGiven SC (5-10 (5-10μμg) twice daily, 30-60 min before mealsg) twice daily, 30-60 min before meals
• It reduces only post meal glucose riseIt reduces only post meal glucose rise
MOAMOA• Stimulates insulin secretion from Stimulates insulin secretion from β- β- cellscells
• Decreases glucagon releaseDecreases glucagon release
AEAE• Diarrhea, nausea, anorexiaDiarrhea, nausea, anorexia
GLP-1 is secretedfrom the L-cellsin the intestine
This in turn…
• Stimulates glucose-dependent insulin secretion
• Suppresses glucagon secretion
• Slows gastric emptying
Long term effectsdemonstrated in animals…
• Increases beta-cell mass and maintains beta-cell efficiency
• Reduces food intake
Upon ingestion of food…
GLP-1 Modes of Action in HumansGLP-1 Modes of Action in Humans
His Ala Glu Gly Thr Phe Thr Ser Asp
Lys Ala Ala Gln Gly Glu Leu Tyr Ser
Ile Ala Trp Leu Val Lys Gly Arg Gly
Val
Ser
Glu
Phe
GLP-1GLP-17
37NH2
Native GLP-1 has short duration of action (t½=2.6 minutes) when given intravenously
DPP IV
Human ileum, GLP-1 producingL-cells
Capillaries,DiPeptidyl Peptidase-IV(DPP-IV)
Adapted from: Hansen et al. Endocrinology 1999:140(11):5356-5363
Native GLP-1 is rapidly degraded by DPP-IVNative GLP-1 is rapidly degraded by DPP-IV
His Ala Glu Gly Thr Phe Thr Ser Asp
Lys Ala Ala Gln Gly Glu Leu Tyr Ser
Ile Ala Trp Leu Val Lys Gly Arg Gly
Val
Ser
Glu
Phe
DPP-IV (DPP4)DPP-IV (DPP4)
inhibitors inhibitors7
37NH2
DPP IV
DPP-IV InhibitorsDPP-IV Inhibitors
DPP-IV InhibitorsDPP-IV Inhibitors
Sitagliptin, Vildagliptin, Sitagliptin, Vildagliptin, Saxagliptin, Septagliptin, AllogliptinSaxagliptin, Septagliptin, Allogliptin• Orally active Orally active
• Selective inhibitors of DPP-IV enzyme that deactivates GLP-1Selective inhibitors of DPP-IV enzyme that deactivates GLP-1
MOAMOA• Increase insulin secretion Increase insulin secretion
• Decrease glucagon releaseDecrease glucagon release
• Delay gastric emptying Delay gastric emptying
• Suppress appetiteSuppress appetite
AEAE• Nasopharyngitis because substance P is also a substrate for DPP-IV, whose Nasopharyngitis because substance P is also a substrate for DPP-IV, whose
levels get elevated, GIT distress and diarrhealevels get elevated, GIT distress and diarrhea
Incretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels increase in response to a meal.
Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and prolonging the actions of these hormones.
Release ofactive incretinsGLP-1 and GIP Blood glucose
in fasting and postprandial
states
Ingestion of food
Glucagon(GLP-1)
Hepatic glucose
production
GI tract
DPP-4 enzyme
InactiveGLP-1
XSitagliptin(DPP-4
inhibitor)
Insulin(GLP-1 and
GIP)
Glucose-dependent
Glucose dependent
Pancreas
InactiveGIP
β cells
α cells
Glucose uptake by peripheral
tissues
30
Mechanism of Action of Sitagliptin Mechanism of Action of Sitagliptin
MOA of DPP IV InhibitorsMOA of DPP IV Inhibitors
Amylin - mimeticsAmylin - mimetics
AmylinAmylin• A hormone co-secreted with insulin from A hormone co-secreted with insulin from β- β- cellscells
• Inhibit glucagon secretionInhibit glucagon secretion
• Delay gastric emptyingDelay gastric emptying
• Suppress appetiteSuppress appetite
PramlintidePramlintide• Stimulates amylin receptor (a G-protein coupled receptor)Stimulates amylin receptor (a G-protein coupled receptor)
• SC before mealsSC before meals
• No hypoglycemiaNo hypoglycemia
AEAE• Nausea, diarrhea, headacheNausea, diarrhea, headache
Kidney as a site of targetKidney as a site of target
SGLT - 2
SGLT-2 InhibitorsSGLT-2 Inhibitors
SGLT-2 InhibitorsSGLT-2 Inhibitors• Newer antidiabetic drugs Newer antidiabetic drugs
• Kidney continuously filters glucose through glomerulous which is reabsorbed Kidney continuously filters glucose through glomerulous which is reabsorbed back from PT by Naback from PT by Na2+2+ glucose co-transporter -2 (SGLT-2) glucose co-transporter -2 (SGLT-2)
• Inhibition of SGLT – 2 decreases glucose re-absorptionInhibition of SGLT – 2 decreases glucose re-absorption
Dapaglifozin, Serglifozin, RemoglifozinDapaglifozin, Serglifozin, Remoglifozin AdvantagesAdvantages
• Weight lossWeight loss
• No hypoglycemiaNo hypoglycemia DisadvantagesDisadvantages
• Because of polyuria there will be more polydipsiaBecause of polyuria there will be more polydipsia
• Increased risk of urinary infection in presence of glycosuriaIncreased risk of urinary infection in presence of glycosuria
• Risk of NaRisk of Na2+2+loss loss
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