Diabetes mellitus

Elaheh Entezar-Almahdi, Pharm.D, Ph.D.

1
Introduction
• Diabetes mellitus (DM) is a group of metabolic disorders
characterized by hyperglycemia and abnormalities in carbohydrate,
fat, and protein metabolism.
• Diabetes is a chronic condition caused by an absolute lack of insulin
or relative lack of insulin as a result of impaired insulin secretion
and action.
• In the long term, these metabolic abnormalities contribute to the
development of complications such as cardiovascular disease
(CVD), retinopathy, nephropathy, and neuropathy and a higher risk
of cancer.

2
 ‫دیابت در ایران‬
‫• از هر ‪ ۲۰‬ایرانی یک نفر به دیابت مبتالست و نیمی از این تعداد نمی دانند که دیابت دارند‪ .‬هر ‪ ۱۰‬ثانیه یک‬
‫نفر در جهان به دلیل عدم آگاهی از دیابت و روش کنترل آن‪ ،‬جان خود را از دست می دهد‪.‬‬
‫• هر ‪ ۳۰‬ثانیه یک نفر در جهان به علت عدم آگاهی از دیابت و روش کنترل آن‪ ،‬پای خود را از دست می دهد‪.‬‬
‫• بر اساس آخرین تحقیقات انجام شده در ایران‪ ،‬از میان جمعیت ‪ ۲۵‬تا ‪ ۷۹‬سال ایرانی‪ ۴/۵ ،‬میلیون نفر به دیابت‬
‫مبتال هستند و از هر ‪ ۴‬فرد دیابتی یک نفر نمی داند که دیابت دارد‪.‬‬

‫‪3‬‬
Classification
• Genetically, etiologically, and clinically,
diabetes is a heterogeneous group of
disorders. Nevertheless, most cases of
diabetes mellitus can be assigned to
Type 1 or Type 2 diabetes.
• The term gestational diabetes mellitus is
used to describe glucose intolerance
that has its onset during pregnancy.
• Early glucose intolerance or prediabetes
is identified as impaired fasting glucose
IFG or impaired glucose tolerance and
they are considered risk factors for the
future development of diabetes.

4
5
Diagnosis
• Criteria for diagnosis of DM include any one of the following:
1. A1C of 6.5% or more
2. Fasting (no caloric intake for at least 8 hours) plasma glucose of 126 mg/dL
(7.0 mmol/L) or more
3. Two-hour plasma glucose of 200 mg/dL (11.1 mmol/L) or more during an oral
glucose tolerance test (OGTT) using a glucose load containing the
equivalent of 75 g anhydrous glucose dissolved in water
4. Random plasma glucose concentration of 200 mg/dL (11.1 mmol/L) or more
with classic symptoms of hyperglycemia or hyperglycemic crisis
• In the absence of unequivocal hyperglycemia, criteria 1 through 3
should be confirmed by repeat testing.

6
Diagnosis

OGTT is not commonly used

(except during pregnancy) owing
to its inconvenience

7
Diagnosis

If the diagnostic test is consistent with

prediabetes , it should be repeated annually.
8
Screening for and diagnosis of GDM

9
 Conversions
• Whole blood glucose (mg/ dL ) =
plasma glucose ( mg/dL ) ÷ 1.12

10
Clinical presentation
• Polyuria
• Polydipsia
• Fatigue
• Weight loss (in type 1 )

11
 ‫عوارض دیابت‬
‫حاد‪:‬‬ ‫•‬
‫کتواسیدوز دیابتی‬ ‫•‬
‫سندرم هایپراسموالر هایپرگالیسمیک‬ ‫•‬
‫هایپوگالیسمی‬ ‫•‬

‫• مزمن‪:‬‬
‫• میکروواسکوالر‪( :‬نفروپاتی‪ ،‬رتینوپاتی‪ ،‬نوروپاتی)‬
‫• ماکروواسکوالر‪( :‬بیماری عروق کرونری‪ ،‬سکته مغزی‪ ،‬بیماری عروق محیطی)‬

‫‪12‬‬
Goals of treatment

• Ameliorate symptoms
• Reduce risk of microvascular and macrovascular complications
• Reduce mortality
• Improve quality of life.
• Desirable plasma glucose and A1C levels are listed in the Table.

13
Components of the treatment

Diet and exercise

Oral hypoglycemic therapy

Insulin therapy

14
Pharmacologic treatment
• ↑ insulin availability (either through direct insulin administration or
through agents that promote insulin secretion)
• Improving sensitivity to insulin
• Delaying the delivery and absorption of carbohydrate from the GI
tract
• ↑ urinary glucose excretion
• Combination of these approaches

➢For patients with overweight, obesity, or a metabolically adverse

pattern of adipose tissue distribution, body weight management
should be considered as a therapeutic target in addition to glycemia

15
Non-insulin agents for type 2 DM

16
Oral glucose lowering agents
• Biguanides → metformin
• Sulfonylureas → glibenclamide , gliclazide
• Thiazolidinediones → pioglitasone
• α Glucosidase inhibitors → acarbose
• Meglitinides (glinides) → repaglinide
• DPP 4 inhibitors → linagliptin , sitagliptin
• SGLT 2 inhibitors → empagliflozin , dapagliflozin
• GLP 1 receptor agonists → liraglutide , exenatide
• Bile acid sequestrants
• Dopamine 2 agonists
• Amylin mimetics

17
Organ targets for glucose lowering medications

18
19
When to start oral agents
• For most patients with A1C >7.5-8 % → pharmacologic therapy
should be initiated at the time of DM 2 diagnosis with lifestyle
modification.
• For those patients who have clear and modifiable contributors to
hyperglycemia and who are motivated to change them → a 3 month
trial of lifestyle modification prior to initiation of pharmacologic
therapy is warranted.
• For highly motivated patients with A1C near target ( ie , 7.5 %), a 3-6
month trial of lifestyle modification before initiating pharmacologic
therapy is reasonable.

20
Choice of initial therapy
• In selecting initial therapy, we consider patient presentation eg ,
presence or absence of symptoms of hyperglycemia, comorbidities,
baseline A1C level), individualized treatment goals and preferences,
the glucose lowering efficacy of individual drugs, and their adverse
effect profile, tolerability, and cost .

• We prefer initiating a single agent (typically metformin) and then

sequentially adding additional glucose lowering agents as needed,
rather than starting with combination therapy.

21
• Newly diagnosed DM 2 are asymptomatic, without symptoms of
catabolism ( eg , without polyuria, polydipsia , or unintentional
weight loss).

• Metformin 500 mg once daily with the evening meal and, if tolerated,
add a second 500 mg dose with breakfast.
• The dose can be increased slowly (one tablet every one to two
weeks) as tolerated to reach a total dose of 2000 mg per day.
• Glycemic efficacy, promotion of modest weight loss, very low
incidence of hypoglycemia, general tolerability, and favorable cost.
• Metformin does not have adverse CV effects, and it appears to
decrease CV events.

22
Contraindications to or intolerance of
metformin
• GI intolerance of metformin → slower titration, ensuring that the
patient is taking the medication with food, or switching to an
extended release formulation may improve tolerability.

• For patients who still cannot tolerate metformin or have

contraindications to it → alternative glucose lowering medication
guided initially by patient comorbidities, and in particular, the
presence of ASCVD or albuminuric CKD.

23
CV or kidney disease
• GLP 1 receptor agonists liraglutide , semaglutide , and dulaglutide
demonstrated favorable atherosclerotic cardiovascular and kidney
outcomes.
• The SGLT2 inhibitors empagliflozin , canagliflozin , and dapagliflozin
have also demonstrated benefit, especially for HF hospitalization,
risk of kidney disease progression, and mortality.

24
• The early introduction of insulin should be considered if there is
evidence of ongoing catabolism (weight loss), if symptoms of
hyperglycemia are present, or when A1C levels > 10 or blood
glucose levels are very high.

• In adults with DM2 , a GLP1 RA is preferred to insulin when possible.

• Insulin + GLP 1 RA → greater efficacy , durability of treatment effect,

and weight and hypoglycemia benefit.

25
Biguanides
• Metformin hydrochloride (glucophage , gly-once)
• MOA: ↓ glucose production from liver, ↓ GI Glu absorption, ↑ insulin
sensitivity
• Dose: 500-2500 mg/day ( qd or tid depending upon preparation)
• ADR: GI ( bloating, anorexia, flatulence, diarrhea and stomach
cramping), metallic taste, lactic acidosis (fatigue, muscle pain,
difficulty breathing ), ↓ B 12 level
• Not recommended in patients with a GFR < 30 ml/min.
• ↓ A1C by 1.3-2.0

26
Dosage forms
• Tab IR 500 , 1000 mg
• Tab XR 500 , 750 , 1000 mg
• Metformin/ glibenclamide (Gliformin,Glucovance) 500/2.5 ,
500/5 mg
• Metformin/ sitagliptin (zipmet) 500/50 , 1000/50 mg
• Metformin/ linagliptin (liroprim) 500/2.5 , 1000/2.5 mg
• Metformin/ empagliflozin (synoripa ) 500/5 , 1000/5 ,
500/12.5 , 1000/12.5 mg
• Metformin/ linagliptin / empagliflozin (glotrio)

27
Meglitinides
• MOA: Insulin secretagogues
• ADR: Mild hypoglycemia, ↑
wt 0.9-3 kg), ↑ LFT
• Contraindicated for use in
patients with DKA.
• Safe in renal and liver
failure.
• Gemfibrozil + repaglinide →
hypoglycemia

28
‫‪Meglitinides‬‬

‫•‬ ‫‪Nateglinide‬‬
‫•‬ ‫)‪Repaglinide (Novonorm, Newbet‬‬
‫•‬ ‫‪Tab 0.5 , 1 , 2 mg‬‬
‫•‬ ‫)‪Dose: 0.5 mg prior to eating up to 4 times a day (max : 16 mg/day‬‬
‫• دارو ‪ ۳۰ - ۱۵‬دقیقه قبل از غذا مصرف شود‪.‬‬
‫• این دارو فقط هنگام مصرف وعده غذایی مصرف شود‪ .‬در صورتی که یک وعده غذایی مصرف نشد دوز قبل آن‬
‫وعده غذایی هم مصرف نشود‪.‬‬

‫‪29‬‬
Sulfonylureas
• MOA: stimulate the release of
insulin from pancreatic β cells and
enhance β cell sensitivity to
glucose
• ADR: hypoglycemia, ↑ wt , GI
(nausea, fullness, bloating)
• ↓ A1C by 1.5-1.7

30
Sulfonylureas
• First generation
sulfonylureas
• Second generation
sulfonylureas
✓ Glipizide
✓ Gliclazide
✓ Tab IR 80 mg
✓ Tab XR 30 , 60 mg
✓ Glyburide (Glibenclamide)
✓ Tab 5 mg
✓ Metformin / glibenclamide
500/2.5 , 500/5 mg
✓ Glimepiride (Amaryl)

31
‫‪How to use‬‬
‫دوز گلی بن کالمید‪:‬‬ ‫•‬
‫شروع با ‪ ۲/۵ - ۵‬میلی گرم روزانه با صبحانه یا اولین وعده اصلی غذا (ماکزیمم ‪ ۲۰‬میلی گرم روزانه)‬ ‫•‬
‫دارو همراه غذا مصرف شود‪.‬‬ ‫•‬
‫جهت کاهش هایپوگالیسمی بیمار دوزهای باالتر از ‪ ۱۰‬میلی گرم دارو منقسم مصرف شود‪.‬‬ ‫•‬
‫دوز گلی کالزید‪۳۰mg MR = 80 mg IR :‬‬ ‫•‬
‫سریع رهش‪ ۴۰ - ۸۰ :‬میلی گرم روزانه )ماکزیمم ‪ ۳۲۰‬میلی گرم روزانه منقسم در ‪ ۲‬دوز(‬ ‫•‬
‫آهسته رهش‪ ۳۰ :‬میلی گرم روزانه با صبحانه )ماکزیمم ‪ ۱۲۰‬میلی گرم روزانه(‬ ‫•‬
‫دارو همراه غذا مصرف شود‪.‬‬ ‫•‬
‫اشکال سریع رهش دارو در دو دوز منقسم و آهسته رهش به صورت تک دوز همراه صبحانه مصرف‬ ‫•‬
‫شود‪.‬‬
‫‪32‬‬
Thiazolidinediones
• Insulin sensitizers (↓ insulin resistance in
muscle and liver)
• MOA: TZDs bind to PPAR γ → regulates
transcription of genes that influence glucose
and lipid metabolism, ↓ TG, ↓ inflammatory
cytokines

• No dose adjustment is necessary in patients

with RF.
• No dose adjustment needed for hepatic
impairment (pioglitazone)
• ADR:
• Hepatotoxicity, Hematologic Effects, ↑ wt (fluid
retention, ↑ peripheral adipose tissue, ↓ visceral
adiposity), Vascular and Cardiovascular Effects
(edema), ↑ bladder cancer, ↑ bone fracture
33
‫‪Thiazolidinediones‬‬
‫•‬ ‫‪Pioglitazone‬‬
‫•‬ ‫‪Tab 15 , 30 , 45 mg‬‬
‫•‬ ‫‪Rosiglitazone‬‬
‫•‬ ‫)‪Dose: 15-30 mg once daily (max: 45 mg/d‬‬
‫• پیوگلیتازون‪:‬‬
‫• دارو با یا بدون غذا مصرف شود‪.‬‬
‫• به بیمار توصیه کنید سطح آنزیمهای کبدی را به صورت دوره ای چک نماید‪.‬‬
‫• در صورت بروز عالئم نارسایی قلبی مصرف دارو متوقف شود‪.‬‬

‫‪34‬‬
α-glucosidase inhibitor
• MOA: reversibly inhibit
glucosidases present in the
brush border of the mucosa →
delays carbohydrate digestion
and subsequent glucose
absorption
• ↓ BA acarbose (< 2%)
• ADR: Flatulence,
diarrhea,abdominal pain, ↑ LFT
• ↓ A1C 0.3-0.7

35
‫‪α-glucosidase inhibitor‬‬

‫‪• Acarbose Tab 25 , 50 , 100 mg‬‬

‫‪• Miglitol‬‬
‫> ‪• Dose: 25 mg TDS (max: 50 mg TDS in wt ≤ 60 kg, 100 mg TDS in wt‬‬
‫)‪60 kg‬‬

‫• آکاربوز‪:‬‬
‫• همراه اولین لقمه غذا مصرف شود‪.‬‬
‫• به بیمار توصیه کنید آنزیمهای کبدی بیمار طی سال اول هر سه ماه و از آن پس دوره ای چک شود‪.‬‬
‫‪36‬‬
DPP-4 inhibitors
• MOA: inhibit the
degradation of GIP and
GLP 1 → ↑ the effects of
these endogenous
incretins on first phase
insulin secretion and
glucagon inhibition

ADR:
Sitagliptin  nasopharyngitis, upper
respiratory tract infection, hypoglycemia,
headache
Linagliptin  hypoglycemia, nasopharyngitis
, diarrhea, and cough 37
 DPP-4 inhibitors

• Alogliptin
• Saxagliptin
• Linagliptin (Lirenta, Melijent ) → 5 mg once daily (±food) → no
dose adjustment in renal failure
✓Tab 5 mg
❑Linagliptin / empagliflozin (Glorenta, Empajent ) 5/10 , 5/25 mg
❑Linagliptin / metformin (Melijent-M) 2.5/500 , 2.5/1000 mg
• Sitagliptin (Ziptin) → 100 mg once daily (±food) → dose
adjustment in renal failure
✓Tab 25 , 50 , 100 mg
❑Sitagliptin / metformin (Zipmet ) 50/500 , 50/1000 mg
38
SGLT2 inhibitors
• MOA: ↓ tubular
reabsorption of glucose
in the kidney , ↑ the
excretion of urinary
glucose
• ↓ Wt , ↑ HDL , ↓ BP, ↑ LDL
• ADR: female genital
mycotic infections and
UTI, DKA

39
 SGLT2 inhibitors
✓Ertugliflozin
✓Dapagliflozin (Gloxiga)
✓Canagliflozin
✓Empagliflozin → 10 mg once daily in the
morning (±food) up to 25 mg once daily
➢ Tab 10, 25 mg
➢ Empagliflozin / linagliptin 10 5 , 25 5 mg
➢ Empagliflozin / metformin (synoripa, jardiplus)
5 500 , 5 1000 , 12.5 500 , 12.5 1000 mg
➢ Empagliflozin / metformin/ linagliptin (Glotrio)
➢ Dose adjustment in renal failure

40
GLP-1 receptor agonists
• MOA: slow gastric emptying,
augment early or first phase
insulin response in response
to elevated glucose
concentrations, ↓ hepatic
glucose production,
suppress appetite
• ADR: GI (nausea, vomiting,
and diarrhea) → dose
dependent, acute
pancreatitis (rare)

41
GLP-1 RA
• Exenatide
• Suspension Reconstituted ER, SC 2 mg
• Dulaglutide
• Semaglutide
• Liraglutide (Victoza, Saxenda)
• Inj 6 mg/ml (3 ml)
• 0.6 mg injected SC into the abdomen, thigh, or arm
once daily for 1 week → 1.2 mg SC daily.
• If the A1C goal is not achieved with a 1.2 mg dose →↑ to
1.8 mg daily

42
Semaglutide (Ozempic® or Wegovy®)
• The FDA-approved dose
for type 2 diabetes has
demonstrated
cardiovascular benefits,
with the exception of
individuals with a history
of HF.
• GI side effects (N/V), the
need for an injection, and
insurance/cost may limit
the use of these agents.

43
Tirzepatide (Mounjaro®)
• A weekly injection for DM 2
• GLP-1 RA
• Manufactured by Eli Lilly.
• Has gained popularity for its
weight loss benefits.

44
Tirzepatide (Mounjaro®)

❑ 2.5 mg SC qWeek ₓ 4 weeks

initially; then increase to 5 mg
SC qWeek.
❑ Maximum Dose: 15 mg SC
qWeek.
❑ No dosage adjustment
required in renal and hepatic
impairment.
❑ Half life: ~ 5 days

45
Amylin mimetic
• Pramlintide
• Amylin analogue
• For type 1 and 2 DM
• SC injection before meals

46
47
48
49
• For all patients consider initiating therapy with a dual
combination when A1C is > %9
• Consider Insulin therapy when BG is > 300-350 and or A1C >
%10-12
• Meglitinides may be used instead of SU in patients with
irregular meal schedules / who develop late postprandial
hypoglycemia on a SU.

50
51
52
Glycemic targets
• Assess glycemic status (A1C or other glycemic measurement such
as time in range or glucose management indicator) at least two
times a year in patients who are meeting treatment goals (and who
have stable glycemic control).
• Assess glycemic status at least quarterly and as needed in patients
whose therapy has recently changed and/or who are not meeting
glycemic goals.

53
Glycemic targets
• An A1C goal for many non pregnant adults of < 7 % without
significant hypoglycemia is appropriate.
• Less stringent A1C goals (such as < 8 % may be appropriate for
patients with limited life expectancy or where the harms of
treatment are greater than the benefits.

54
Microvascular Complications

• Nephropathy (ACEI,ARB,SGLT2 inhibitors)

• Autonomic Neuropathy (Prokinetics)
• Peripheral Neuropathy (TCAs, SNRIs, Antiepileptics, Capsaicin);
Only pregabalin and duloxetine have the FDA approved indication for
the treatment o fDPN; others are off label
• Diabetic Foot Infection (Skin, foot, and sore care)

55
Insulins

56
Insulin
• Insulin is a hormone secreted from the pancreatic β cell in response
to glucose and other stimulants (e.g., amino acids, free fatty acids,
gastric hormones, parasympathetic stimulation, β adrenergic
stimulation).
• The hormone is made up of two polypeptide chains (a 21 amino acid
A chain and a 30 amino acid B chain), which are connected by two
disulfide bonds
• Difference in their physical, chemical properties and
pharmacokinetics

57
Pharmacokinetics: Absorption,
Distribution, and Elimination
• SC injection
• Regular insulin → IV, IM, or SC
• Afrezza (insulin human) → is the only insulin currently available as a
powder for inhalation.
• Variations in SC absorption can occur, primarily related to changes
in blood flow around the injection site.

58
 Elimination
• Endogenous insulin → cleared by the liver in nondiabetic individuals (60%) with
the kidneys removing only 35-40% of it.
• Exogenous insulin → up to 60% is cleared from the systemic circulation by the
kidneys, with the liver accounting for only 30-40% of its clearance.

59
Insulin pharmacokinetics
• Clinically, the most important
differences among insulin
products relate to their onset,
peak, and duration of action.
✓ Rapid acting (Lispro, Aspart,
Glulisine, Afrezza)
✓ Short acting (Regular)
✓ Intermediate acting (NPH)
✓ Long acting (Detemir, Glargine,
Degludec)
• Insulin is made through
recombinant DNA technology.
• Only regular and NPH → human
insulin
• All other insulins are human
insulin analogs.

60
61
Lispro (Humalog®)

• The first available rapid acting insulin analog.

• The natural amino acid sequence of the insulin B
chain at positions 28 (proline ) and 29 (lysine) is
inverted to form lispro.
• It can be injected shortly before eating (0-15
minutes) → Within 15 minutes before or
immediately after a meal.
• These insulins lower 2-hour postprandial BG
levels and can decrease the risk of late
postprandial and nocturnal hypoglycemia
compared with regular insulin formulations.

62
Lispro (Humalog®)

• Age ≥ 3 years
• Pregnancy category B
• 100 IU/ ml ( 3 , 10 ml) (vial, pen)
• Humalog mix 25/75, 50/50 (100 IU/ml) ( 3 ml)

63
Aspart (Novorapid ®, Novolog®)

• Differs from human insulin by substitution of

aspartic acid at B 28 .
• Age ≥ 2 years
• Pregnancy category B
• Dosage form: 100 unit/ml ( 3 ml) vials and
prefilled pen (FlexPen)
• ‫ نارنجی‬/ ‫قلم سرمه ای‬

64
 Glulisine (Apidra ®)

• Differs from human insulin by

substitution of lysine for asparagine at
position B 3 and
• glutamic acid for lysine at position B 23
• Age ≥ 4 years
• Pregnancy category C
• Dosage form: 100 IU/ml (3 ml) vials and
prefilled pen (Solostar)

65
Insulin-short acting
• Regular insulin (Humulin R and
Novolin R)
• Physiologic Insulin (Crystal Insulin)
• Mostly used for postprandial glucose
control
• SC, IM, IV
• Vial 100 units/mL (10 ml)
• The 30-60 minute onset of action
requires proper timing of premeal
regular insulin, which is difficult
for most patients.

66
Rapidly acting analogues vs regular
• Twice the maximal concentration and takes about half the time to
reach the maximal concentration.
• Peak insulin action occurs approximately twice as fast with the
analogues as with regular insulin.
• less variability in absorption at the injection site and possibly in
less variation between and within patients.
• Less immunologic reactions
• Less postabsorptive hypoglycemia

67
Inhaled insulin
• Insulin human powder for inhalation ( Afrezza ) is a rapid acting
insulin indicated for postprandial coverage in patients with Type 1 or
Type 2 diabetes.
• It is produced using recombinant DNA technology and is supplied
via inhaler that is breath activated by the patient.
• The insulin in the Afrezza inhaler is regular human insulin , and
metabolism and elimination are similar to that of regular insulin
following pulmonary absorption.

68
 Inhaled insulin

• The pharmacodynamic profile of inhaled Afrezza is similar to that of

rapid acting insulin.
• It is pregnancy category C and has not been studied for use in
patients < 18 years old.
• Insulin human powder for inhalation is available as prefilled inhalers
containing 4 , 8 , or 12 units of rapid acting insulin to be used at the
beginning of a meal.
• It is contraindicated for use in patients with chronic lung disease
such as asthma and chronic obstructive lung disease as well as
current smokers.
69
Insulin-intermediate acting
• Insulin Isophan(NPH)
• Insulin R + prothamin
• Humulin N or Novolin N

• Hypoglycemia more than long acting insulins

• Twice daily for basal glucose control

• NPH, neutral protamine Hagedorn , or isophane insulin suspension

• Vial 100 IU/ml ( 10 ml
• Dose in DM 2 : 0.1 to 0.2 units/kg/day

70
Glargine (lantus , Toujeo , Basaglar , Basalin)

• Long acting insulin

• Pregnancy category C
• Pen 100 IU/ml ( 3 ml), 300 IU/ml ( 1.5 ml)( Toujeo ) vial and a prefilled pen Solostar.
• It is approved for once daily SC administration for the treatment of adult and
pediatric patients (age ≥ 6 year).
• Toujeo has not been studied for use in the pediatric population.

71
Insulin glargine
• It can be administered any time during the day, but it is important to take it at the
same time each day → bedtime or, less commonly, in the morning
• Insulin glargine is an insulin analog in which asparagine in position A 21 is
substituted with glycine and two arginines are added to the C terminus of the B
chain.
• → shift in the isoelectric point from PH 5.4 to 6.7 , making it more soluble at an
acidic pH.
• Peakless insulin
• Lowest risk of hypoglycemia
• Use for basal glucose control
• Once to twice daily

72
Insulin glargine
• Once injected, insulin glargine (which is a clear solution with a pH of
4.0 ) → precipitates at physiologic pH → depot that releases insulin
slowly for up to 24 hours.
• Zinc is added to further prolong the duration of insulin glargine.
• Insulin glargine is associated with more injection site pain compared
with NPH which is likely related to its acidity.

73
Insulin Toujeo (U300)
• Store prefilled pens that have
been opened (in use) at <30°C and
use within 56 days
• Used to control high blood sugar
in adults and children who are 6
years of age and older with DM.
• 1 cc = 300 U
• I vial (1.5 cc)= 450 U

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Differences
between
toujeo and
lantus

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Insulin detemir (levemir)
• Long acting
• Is approved for once or twice daily SC administration for the
treatment of adult and pediatric patients ( age ≥ 2 years)
• Pregnancy category B
• B 30 threonine has been removed and the B 29 lysine residue has
been covalently bound to a 14 carbon fatty acid → more slowly
absorbed in the SC tissue because the fatty acid moiety binds to
albumin, creating a long acting insulin.

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Insulin detemir (levemir)
• Insulin detemir is a neutral
• 100 IU/ ml ( 3 ml)
• Insulin detemir’s kinetics and dynamics are
dose dependent
• DM 1 → two injections daily are usually
required to provide adequate basal coverage
due to a smaller insulin dose requirement in
this patient population.
• Insulin detemir demonstrates less
intrasubject variability than NPH or insulin
glargine.
• Once punctured (in use), vials may be stored
under refrigeration or at room temperature
<30°C (<86°F); use within 42 days.
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Insulin degludec (Tresiba®)
• long acting basal human insulin analog approved in the US in 2015 for once daily
SC administration.
• It is pregnancy category C and is not indicated for use in the pediatric population 1
year of age and older.
• Insulin degludec differs from human insulin in that the amino acid threonine in
position B 30 has been omitted and a side chain consisting of glutamic acid and a
C 16 fatty acid has been attached.

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Insulin degludec (Tresiba®)

• Insulin degludec has a much longer

duration of action (> 42 hours)
• Prefilled pen (FlexTouch device)
100, 200 units/ mL.
• The FDA has also approved a
combination insulin degludec
/insulin aspart 70/30 combination (
Ryzodeg 70/30 ) which is intended to
be used once to twice daily prior to
a main meal.

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Type 2 diabetes dosing for Tresiba®

82
Type 1 diabetes dosing for Tresiba®

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Insulin degludec + liraglutide
(Xultophy®)
• SC injection
• 3.6 mg/100 units per mL
• Available as a 3-mL single-use pen
• For DM-2
• The pen delivers doses from 10-50
units with each injection
• Each dosage unit contains 1 unit
of insulin degludec and 0.036 mg
of liraglutide.

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NPH + Regular (70/30)
70 unit NPH + 30 unit Regular

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Humalog mix
• Insulin lispro and insulin aspart
have been cocrystallized with
protamine to create an
intermediate acting insulin similar
to NPH.
• Humalog Mix 75/25 lispro
protamine/Lispro ) and Humalog
Mix 50/50 lispro protamine/lispro)

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NovoLog Mix, Novomix
• NovoLog Mix 70/30 is aspart
protamine and insulin aspart in a
fixed ratio of 70:30.
• These premixed insulins are
useful for patients who have
difficulty measuring and mixing
insulins and are dosed twice daily
• 100 units soluble insulin aspart
*/protamine crystallised insulin
aspart * in the ratio 30/70 /ml 3 ml)

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Multiple insulin injection
1. Estimating total daily insulin requirements for Type 1 DM
• 0.4-1 U/kg
2. Estimating basal insulin requirements
• 50% total daily dose
• Another 50% is divided into 3 premeal insulin.
• Add 1 unit to insulin short acting or rapid acting for every 50 mg/dL higher BG
from the target BG level.

3. Estimating total daily insulin requirements for Type 2 DM

• 0.2-0.4 U/kg

• For NPH- regular insulin: 2/3 of total daily dose in the morning and
1/3 in the evening
• Provide a 2:1 ratio of NPH: regular in the morning and evening

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Switching between products

96
Switching between products

97
Switching between products

98
Switching between products

99
100
Insulin Adverse Effects

• Lipoatrophy
• Lipodystrophy
• Weight gain
• Hypoglycemia

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Hypoglycemia treatment

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103
‫مکمل های موجود در ایران مخصوص افراد دیابتی‬
‫• کرومیوم‬
‫• جین سینگ‬
‫• دارچین‬
‫گالگا‬ ‫•‬
‫شنبلیله‬ ‫•‬
‫بیترملون‬ ‫•‬
‫بنفوتامین‬ ‫•‬

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Thank you for your attention…

Any questions?
E-mail:
elaheh.entezarmahdi@gmail.com

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