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