Insulin22
Upcoming SlideShare
Loading in...5
×
 

Insulin22

on

  • 4,325 views

ALL ABOUT INSULIN FROM HISTORY TO PRESENT TRENDS OF USE...

ALL ABOUT INSULIN FROM HISTORY TO PRESENT TRENDS OF USE...

Statistics

Views

Total Views
4,325
Views on SlideShare
4,325
Embed Views
0

Actions

Likes
5
Downloads
222
Comments
0

0 Embeds 0

No embeds

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Insulin22 Insulin22 Presentation Transcript

  • INSULIN
    Dr.Nagula Praveen
  • Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates, so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life. 
    — Sir Frederick Grant Banting'Diabetes and Insulin', Nobel Lecture, 15 September 1925. In Nobel Lectures: Physiology or Medicine, 1922-1941 (1965), 68. 
  • Laughter is the best medicine - unless you're diabetic, then insulin comes pretty high on the list. Jasper Carrott 
  • Introduction
    Is a protein
    Synthesised from the beta cells of islets of langerhans.
    Deficiency causes DIABETES MELLITUS.
    Gene located on chromosome 11.
    Name 'insulin'by J de meyer .-1907.
    Insulin –first hormone for which radioimmunoassay was developed.
    Name ''insulin'' is derived from word insula—meaning island---a latin word.
    Connaught initial name
    Novo nordisk –since 1923
  • History
    1869---Paul Langerhans–two distinct group of cells in pancreas –acinar cells ,islets.
    1889---Minkowski---pancreactomized dogs—diabetes mellitus.
    1921—Frederick Grant Banting–insulin secreted was destroyed by proteolytic digestion
    Charles .H.Best, a fourth year medical student –ligated the pancreatic ducts
    Leonard Thompson, a 14 yr old was the first person to receive insulin .---11 JAN 1922
    J.M.Collip-who purified epinephrine,purified insulin also.
    Purified and crystallized –Abev
    Aminoacid sequence by Sanger—1960
    Complete synthesis of protein-1963
    3 dimensional structure—Hodgkins-1971
    NOBEL PRIZE in medicine or physiology-1923-Banting and Best,Mcleod and Collip
  • Best and Banting
  • BANTING AND BEST
  • Leonard thompson
  • V.SHESHAIH
  • Secretion of insulin
    Β cells of islets of langerhans in the pancreas—secrete 110 AA chain ,single chain—PREPROINSULIN.
    Rough endoplasmic reticulum---24 AAterminal( NH2)of preproinsulin is cleaved off—PROINSULIN
    During formation of PROINSULIN,the molecule folds,disulfide bonds are formed
    Converted to INSULIN-golgi complex.
    During conversion –4 basic AA are removed,remaining connector or C peptide removed byproteolysis.
    Insulin formed is stored in vesicles.
    Bound to zinc atoms.
    Exist in hexamer form.
  • Structure of insulin
    51 amino acids
    5808 daltons
    2 peptide chains A and B
    One intrasubunit and two intersubunit disulphide bonds
    A-21 AA,B-30 AA
    Slight difference in structure in species
    Porcine-one AA
    Bovine—3 AA
    C peptide differs in all.
  • Equimolar amounts of C peptide,insulin are released into the circulation.
    C peptide has no biological function.
    It is useful index of insulin secretion.
    Proinsulin-insulin by 2 Ca endopeptidases
    PC2 lysine arginine—C-A
    PC3 argininearginine –C-B
  • Structure of insulin
    Conserved portions of insulin—3 disulfide bonds
    Both ends of A chain
    C terminal residues of B chain
  • INSULIN STRUCTURE
  • Genetics of insulin
    Single insulin gene –chromosome 11
    Close to IGF-1
    Single protein product in most species
    2 genes encode—rat,mice---two molecules differ from each other by 2 AA residuesin B chain.
    Several  helical regions in both A and B chains.
    Proinsulin –INS gene
  • Existence of insulin
    Isolated chains of insulin are inactive.
    In acid solution –dimers
    At neutral Ph—exist as hexamers and with Zn.
    Insulin in solution exists as monomer,dimer,hexamer
    Intermediate,long acting insulins have hexamers are common
    2 molecules of zn are incorporated in hexamer .
    Zn plays a role in crystallization.
    Monomer is active.
  • Pharmacology of insulin
    Introduction of insulin of human insulin,proinsulin gene into organisms—e.coli,yeast-recombinant DNA technology.
    Insulin ppt at ph—5.4—soluble at 2-3
    1 U of insulin -38.5 ug of substance
    40 U and 100 U –40u/ml,100u/ml
    10 U for infants
    T1/2—40 min
  • NN= SaccharomycesCerevisiae
    Eli lilly= non-disease producing strain of E.Coli
    Sanofi= non-disease producing strain of E.Coli
  • Insulin receptor
    Insulin binds to N and C terminal of  subunit of the receptor.
    cysteine rich region in alpha subunit.
    Affinity towards receptor-effect on glucose metabolism.
    Insulin is a member of IGF s.
    IGF1,IGF2 –are similar to proinsulin ,concerned with growth,Cpeptides are not removed.
    IGF1 –somatomedin,growth promoting actions of insulin.
    Proinsulin has 2% metabolic potency of insulin,50% as potent for mitogenesis---atherosclerosis
  • hexamer
  • After injection
  • Regulation of insulin secretion
    Prinicipal stimulus for insulin secretion is the glucose.
    Sugar is more effective in provoking insulin secretion when taken orally than when taken IV –inc vagal activity.
    Stimulants—various nutrients-glucose,AA,FA,ketones.
    GI hormones
    pancreatic hormones
    autonomic neuro transmitters
    2 adrenergic receptor—inhibits insulin receptor.
    Β2 adrenergic receptor,vagal—release.
    Hypoxia,hypothermia,surgery,severe burns—suppress insulin secretion.
    2 antagonists—increases insulin
    B2 antagonists—decreases insulin
    HORMONES—GLP-1,GIP-inc insulin
    Similarly gastrin,secretin,cholecystokinin,VIP,GRP,enteroglucagon
  • Insulin secretion is BIPHASIC.
    First phase—peak at 1-2 min,short lived.
    Second phase-delayed onset,long duration.
    Depends on intracellular calcium
    Intracelular Ca—increased by phospholipase C by Ach,cholecystokinin
    Inc c AMP-b adenylcyclase---GLUCAGON.
    Insulin circulates in blood as monomer.
    Distributed in ECF..
    Aminoacid which causes secretion of insulin –arginine.
    Glucokinase acts as glucose sensor.
    Glucose conc <90mg/dl—no insulin release
  • Rate of secretion in fasting—1U of insulin /hr into portal vein
    Conc of insulin 2-4 ng/ml.50-10031U/ml-portal vein
    Peripheral circulation—0.5ng/ml,12U/ml.
    Goal of insulin therapy is to mimic this pattern –diificult to achieve with SC injection.
    T1/2-insulin 5-6 min in normal subjects
    Increased in diabetes
    Proinsulin -17 min
    C peptide -30 min serves as a marker of insulin secretion
  • degradation
    Liver,kidney,muscle
    50% insulin that reaches liver is destroyed.
    It is filtered by glomeruli-reabsorbed by tubules –degrade it
    Renal function impairement appears to affect the rate of disappearance of circulating insulin to a greater extent than hepatic disease
    Degraded in endosomes of liver.
    Thiolmetalloproteinases in liver,muscle,kidney,brain
    insulinase
  • Functions of insulin
    Globally—
    Control of cellular intake of certain substance-glucose in muscle,adipose tissue.
    Increase of DNA replication and protein synthesis
    Modification of activity of numerous enzymes.
  • Cellular level
    Increased glycogen synthesis.
    Increased fatty acid synthesis.
    Increased esterification of fatty acids
    Decreased proteolysis
    Decreased lipolysis
    Decreased gluconeogenesis
    Decreased autophagy
    Increased aminoacid uptake
    Increased potassium uptake
    Relaxes arterial muscle tone,increases blood flow-micro arteries
    Increases HCL secretion in stomach.
  • Types of insulin
    20types of insulin products available in four basic forms,each with a different time of onset and duration of action.
    Which to choose is individulaised
    Choosing insulin depends on
    Onset-how soon it starts working
    peak time-when it works the hardest
    Duration-how long it lasts in the body.
    Obesity affects the work of insulin in the body.extra fat tissue –more resistant to insulin.
  • Types of insulin
    Five different types
    Some are clear in appearance .,some are cloudy
    RAPID ONSET-FAST ACTING INSULIN-novo rapid (insulin Aspart)
    humalog (Lispro)
    SHORT ACTING INSULIN—actrapid,Humulin,hypurin neutral(bovine)
    INTERMEDIATE ACTING INSULIN-cloudy—protamine or zinc added
    Protamine—protaphane,humulinNPH.hypurinisophane
    MIXED INSULIN—RAPID/INTERMEDIATE—novomix 30,humalog mix 25,mixtard 30/70,mixtard 20/80
    30/70—30% is short acting,70% long acting
    LONG ACTING INSULIN-lantus-(glargine).levemir(detemir)
  • Insulin sliding scale
    Not recommended for subcutaneous injection
    50U -50 ml NS
    Every one hour until the blood glucose level stabilises
    Rate of infusion adjusted as per blood sugar.
    <120mg/dl-no insulin
    120-200---2U/hr
    200-300—3U/hr
    300-500---5U/hr
    >500---7U/hr
    -JAPI october 2007
  • Somoygi phenomenon
    Somogyi effect is a rebounding high blood sugar that is a response to low blood sugar.
    It is due to counteracting hormones release –glucagon,adrenaline,cortisol
    Frequent monitoring of blood glucose
    Night dose to be low compared to morning dose.
  • Dawns phenomenon
    Early morning hyperglycemia without nocturnal hypoglycemia.
    It is due to counter regulatory hormones
    No need of insulin dose change.
  • Increasing requirements
    Infection,stress,puberty,pregnancy,acromegaly,cushings syndrome.
    Lipohypertrophy at the site of injection
    Malignancies
    Compliance of the patient
  • Decreaesing requirements
    Impending renal failure
    Honeymoon phase in type 1
    Hypothyroidism
    Addisons disease
    Hypopituitarism
    Remission of diabetes
  • In renal disease
    Half of the sliding scale of insulin dose to be given
    As insulinase enzyme does not function
    The duration of insulin action increases.
  • Indications for insulin therapy
    Type 1 diabetes
    Women with diabetes who become pregnant or are breastfeeding
    Transiently in type 2 diabetes in special situations- renal & hepatic disease, pancreatitis, HHS, during surgery, infections etc.
    In type 2 diabetes, inadequately controlled on OADs
  • Side effects of insulin use
    Hypoglycemia
    Weight gain
    Locally-allergy
    infection
    abscess
    anaphylaxis
  • Insulin devices
    Insulin syringes
    Delivery pens
    Insulin pumps
    Insulin syringes—10ml insulin vials
    30 unit—0.3 ml,50 unit-0.5 ml,100 unit-1ml
    Needles -8mm to 13mm
    Use each syringe only once.
    Insulin pen-insulin catridge-3ml-300units fits into the device
    Disposable, reusable
    Durable pens are—Novopen3,Novopen demi,Innovo and HumaPen
    Pre filed disposable devices –innolet,flexpen and Novolet.
  • Insulin pumps-reservoir of insulin-infusion set
    worn outside the body—abdomen
    Only short or rapid acting insulin are used—mimics physiological pattern
    Inhaled insulin
  • Mode of administration
    Subcutaneous
    Intravenous
    Inhaled
    Intramuscular
  • Subcutaneous injection
  • Sites
    Rotation of injection site to prevent lipohypertrophy.
    Within one area.
    Abdomen has fastest rate of absorption
    Exercise increases
    lipohypertrophydecreasees
    Rate of absorption after IM is faster.
  • Sites of injection
  • syringes
    1ml most common
    26-31 guage needle
    30 or 31 bend in single use
    No sharing of needles
    Reuse is widely practiced
    Infection---poor hygeine,concurrent illness
  • Insulin syringe and vial
  • Timing of insulin
    30 min prior to meals
    Not to exceed 30 min in case of rapidly acting insulins
    Intermediate acting insulin –bed time.
  • Insulin injection
    Cloudy insulin gently rolled in between
    Pen needs to be rotated upside down for at least ten times before using
    Air of volume equal to dose of insulin should be injected in vial.
    No use of alcohol may destroy silicon coating.
    90 angle—thin 45 
    Routine aspiration not needed
    Embedded for 5 sec after complete depression--pens
  • Alternative routes—failed
    Jet injectors—deliver high pressure stream of insulin.
    Useful in lipoatrophy.
    Transdermal
    Iontophoresis
    Low frequency ultra sound
    Transferomes—phosphatidylcholine vesicles
    50% SC efficiency
  • Intranasal
    Bioavailability is 8-15%
    Nasal irritation is common
    High rates of treatment failure.
    Gelified nasal insulin
    Oral
    Enteric—limited bioavailability
    Too large,hydrophilic
    Only 0.5% reaches circulation
    Buccal—aerosol solution
    • Pulmonary—large surface area—premeal delivery
    Lung cancer risk
  • Thank you
  • Types of insulin
  • Types of insulin and action
  • Regular insulin
    Clear solution at neutral pH
    0.4% zinc added-hexamers
    Phenol or cresol-prevent growth of microorganisms
    Onset of action within 15-30 min after SC
    max activity-120 -150 min
    Action -6-8 hrs
    Insulin to be given 30-40 min prior to meals
  • indications
    In case of type1 DM ,type 2 DM –DKA,HONK,Pregnancy,patients being taken up for surgery,acute illness.
    Controls post prandial blood glucose levels when used with long acting insulins.
  • NPH or isophane insulin
    At hagedorn university in 1940.
    Protamine added in 1:6 ratio to regular insulin
    Phosphate buffer for neutral ph
    Zinc ,cresol.
    Peak of action at 5-7 hrs
    Action lasts for 12-15 hrs.
    Bed time to control FBS.
    Cloudy.
  • Lente insulin
    Zinc in amounts 10 times to NPH
    Acetate as buffer
    Insoluble zinc insulin complexes
    Semilente---amorphous,biphasic absorption
    Ultralente—long acting crystalline suspension
    Can’t be mixed with regular insulin.
  • Premixed formulations
    30:70
    50:50
    25:75
    Regular and NPH insulin
  • Rapidly acting insulins—insulin analogues
    Analogous to keep insulin in monomeric form
    Only change in aminoacid sequence at a particular point.
    Action starts within 15 min after SC injection.
    Peaks at 60-90 min
    Over by 4 hrs
    Post prandial excursions curtailed
    No delayed hypoglycemia.
  • Aspart
  • Aspart
    by Novo Nordisk as Novolog or Novorapid
    B28 ---proline is substituted by aspartic acid residue.
    Increased charge repulsion—no hexamers
    Components-
    zinc-metal ion19.6g/ml
    buffer-disodium hydrogen phosphate dihydrate1.25 mg/ml
    Preservative-- m cresol 1.72mg/ml Phenol 1.50mg/ml
    Isotoncity agent –glycerin and Nacl
    ph 7.2-7.6
  • NovoRapid (Insulin Aspart )
    Pro
    Phe
    Gly
    Arg
    Phe
    Asp
    Tyr
    Glu
    B20
    Thr
    Gly
    Asp
    Cys
    Lys
    B28
    B30
    Thr
    Val
    Asn
    Cys
    A21
    Tyr
    Leu
    A1
    Gly
    Asn
    Tyr
    Ile
    Glu
    Leu
    Val
    Leu
    Ala
    Glu
    Gln
    Glu
    Gln
    Tyr
    Val
    Leu
    Cys
    Ser
    Cys
    Leu
    Ile
    Ser
    Thr
    Cys
    His
    Ser
    Gly
    Cys
    Leu
    B1
    His
    Gln
    Asn
    Val
    Phe
  • Lispro
  • Lispro
    Marketed by Eli Lilly—HUMALOG
    First insulin analogue.
    Penultimate lysine and proline residues on the Cterminal end of B chain are reversed---no change in receptor binding.
    No formation of hexamers
    Post prandial excursions are controlled.
  • Glulisine
  • Glulisine
    Marketed by sanofiaventis. APIDRA
    Asparagine is replaced by lysine at B3
    Lysine replaced by glutamic acid at B29
    3B-lysine-29B-glutamic acid-human insulin
  • Long acting insulin analogues
    Steady basal insulin levels
    Glargine –isoelectric at 7.4
    Clear and soluble at acidic ph
    Ppt after SC injection
    Action >24 hrs
    Detemir—fatty acid chain attached to it.
  • Glargine
  • Glargine
    Marketed by sanofiaventis—Lantus
    Resembles basal insulin secretion of non diabetic pancreatic beta cells.
    Controls fast blood glucose.
    Glycine for asparagine at A21 and two arginine added to carboxy terminal of B chain.
    Formulated at acid pH—4.0
    Hexamers at pH-7.4
    Can be injected with I port
  • Glargine
    In 2009 there was conflicting and confusing data regarding the link of glargine insulin and cancer developing risk.
    ADA –the avaailable data does not provide a cause for concern and that changes to the prescribing advice are therefore not necessary.
  • Detemir
  • C14 fatty acid chain
    (Myristic acid)
    Phe
    Gly
    Phe
    Arg
    Glu
    Tyr
    Thr
    Gly
    Pro
    Cys
    Lys
    Val
    Thr
    Lys
    Cys
    Asn
    A21
    B29
    Leu
    Tyr
    Gly
    A1
    Asn
    Tyr
    Ile
    Glu
    Leu
    Val
    Leu
    Ala
    Glu
    Glu
    Gln
    Gln
    Tyr
    Val
    Cys
    Leu
    Leu
    Cys
    Ser
    Ser
    Thr
    Cys
    Ile
    His
    Ser
    Gly
    Cys
    Leu
    Gln
    His
    Asn
    Val
    Phe
    B1
    Design of Insulin Detemir - 1
    LysB29(N-tetradecanoyl)des(threonine)human insulin
    Des-threonine myristic(mir) acid
  • Detemir
    Marketed by Novo Nordisk –LEVEMIR
    Fatty acid myristic acid is bound to lysine aminoacid at B29.
    quickly absorbed—binds to Albumin—complex
    Better control of blood glucose levels
    Appreciable decrease in HbA1c levels--
  • levemir
    Albumin binding: Makes Levemir therapy with a smooth and peakless profile throughout the day
  • Time-action profile
    Up to 24 hours
    Predictability
    lower within-patient variability than NPH and glargine
    Glycaemic control
    Better glycaemic control
    Hypoglycaemia
    Lesser hypoglycaemia compared with NPH & glargine
    Weight
    No undesirable weight gain shown in all studies
  • Premixed analogue
    Protamine insulin +rapidly acting analogues.
  • Strength of insulin
    40 U /ml –most widely used
    WHO—all insulin across the globe to be U 100.
    Storage
    Refrigerated
    <2 and >30 C
    Excess agitation avoided
    Used for > 1 month –may lose potency.
    Away from sunlight.
  • Mixing insulins
    glargine is not mixed with any other insulin.
  • Problems with syringes / vials
    Cumbersome procedure
    Difficult to transport and carry around
    Inaccuracy in withdrawing the correct amount of insulin
    Difficulty in mixing insulin
    Insulin wastage
    Stigma of injections and hence suggestion of ill-health
    Needle passes a rubber membrane and losses sharpness-more pain
  • Advantages with Devices
    Simplicity - Simple to operate and inject
    Accuracy - A new superior standard in dose accuracy
    Reliability - High quality materials and finish
    Discreeteness - Non-medical, non-syringe design
    All-in-one - Pen + insulin cartridge + needles
    Portability - Small & compact, robust carrying case - with space for extra needles and cartridge
  • Device vs. Syringe
  • Prefilled pen
    Contain a built-in, single-use insulin cartridge
    Loading
    Require no loading by patient
    Ease of use
    Portable, durable, & lightweight delivery systems
    patients who have difficulty handling the
    cartridges in reusable pens
    persons with busy schedules
    short - term therapy = GDM, Post-Surgery
    Ease of disposal
    are made of non-polluting plastic
    it breaks down into naturally occurring substances when burned industrially
    it can be safely landfilled
  • FlexPen®
    Easy to use
    • dialling dose; accurate / reliable
    • good control during injection
    • ‘can hear clicks’
    • minimal pressure required
    • can be administered with one hand
    Easy to read (white font on black)
    • numbers clearly visible
    • safer because mistakes less likely
    Convenient; pre-filled / no re-loading
    • easy to attach needles
    • easy to teach
    Portable and discreet
    • comes in carry case
  • FlexPen®
    FlexPen® is a unique dial-a-dose insulin pen. You can dial doses from 1 to 60 units inincrements of 1 unit
    • Single unit increment
    • Easy dial back
    • Large & easy to ready display
    • Max single dose-60 U
    • Virtually painless 31G needle
    FlexPen- Easy to use and teach
  • Design Characteristic of FlexPen
    The FlexPen is a disposable, prefilled insulin delivery device— there is no insulin cartridge to change.
    The FlexPen is simply thrown away when the last of the insulin has been used, or at the end of the in-use time.
  • FlexPen Prefilled syringes are available with three insulin analog preparations: Levemir, NovoRapid, and NovoMix 30.
    Each FlexPen is named for the insulin it contains and is color branded for easy identification.
    • LevemirFlexPen = identified by green push button
    • NovoMix 30 FlexPen = identified by Blue push button
    • NovoRapidFlexPen = identified by orange push button
  • Durable pen
    Patient has to insert an insulin cartridge into pen's delivery chamber
    Flexibility
    Allows greater flexibility for some patients
    Changing types of insulin without needing to buy another pen if prescription changes
    Ease of use
    Durable and easy to use
    Designed for longer duration of use.
    With individual use - risk of infection is minimized
  • NOVO NORDISK
  • Insulin dose calculation
    Calculate total daily insulin TDI
    0.5 *WEIGHT (KG) or sum of current doses
    Ex—60 kg---30U.
    Total meal time insulin—lispro,aspart,regular
    60% 0f TDI
    18U-----three divided doses—breakfast,lunch.dinner
    Total basal insulin—NPH,glargine,ultrlente
    40% of TDI
    12U---bed time insulin
  • Insulin dosage
    DKA
    Bolus dose—IV 0.1U/kg
    IM-0.3U/kg
    Then 0.1U/kg/hr
    Mild episodes of DKA—short acting insulin analogues
    IV regular insulin to be used in infusion until acidosis resolves
    0.05-0.1U/kg/hr.
  • Pre prandial insulin dose
    INSULIN /CARBOHYDRATE ratio
    1-1.5 U/10 gm of carbohydrate
    Supplemental or correcting insulin—1Uof insulin for every 50mg/dl of glucose over the preprandial glucose target.
    Ex
    A 60kg male has FBG 0f 250 mg/dl,desired is 100mg/dl,the insulin dose is 60*(250-100)/1500
    60(150/1500-----60*150/1500----6U
  • Twice daily regimens
    Long acting insulinNPH.regular insulin –morning,bed time.
    2/3 of insulin in the morning
    1/3 of insulin at bed time
    To prevent nocturnal hypoglycemia.
    FBG-prior evening long acting insulin
    Pre lunch glucose—morning short acting insulin
    Pre supper glucose-morning long acting insulin’
    Bed time—pre supper short acting insulin.
    Not an optimal regimen for 1 DM
  • Continuous subcutaneous insulin infusion CSII
    Very effective insulin regimen for type 1 DM
    To the basal infusion,,a pre prandial insulin bolus is delivered by the device based on instructions from the patient—who uses an individualized algorithm incorporating the preprandial plasma glucose and anticipated carbohydrate intake.
    Sophisticated device
    Advantages:
    programmed dose
    basal infusion rates altered during exercise
    different doses of insulin can be matched based on meals
    reqiures education of the patient and frequent interactions
    Disadvantages---infection,hyperglycemia,DKA
    Short acting insulin analogues are used.
    SBMG
  • EXUBERA
  • SEP 2006-OCT 2007
    Powdered form of recombinant human insulin
    Effective but no better than short acting insulin.
    Discontinued because of poor sales.
    Marketed by pfizer.
    1mg-3U
    Increment is not linear
    1mg given subsequently is more insulin than 3 mg given once.
    3mg—8U
    May be associated with lung cancer
    not Cost effective
    Mannkind --AFREZZA
  • Drug interactions
    Enhances blood glucose lowering effect---OAD,ACEI,disopyramide,fibrates,fluoxetine,MAOI,pentoxyfilline,propoxyphene,salicylates,sulphonamides.
    Reduces blood glucose lowering effect—corticosteroids,danazol,diazoxide,diuretics,glucagon,isoniazid,etrogens,phenothiazine,somatropin,salbutamol.
  • Thank you
    sagittarian