ORAL DRUGS FOR DIABETES WITH AACE 2023 GUIDELINES

1. ORAL HYPOGLYCAEMIC DRUGS
OHA & AACE GUIDELINES 2023
ORAL ANTI HYPERGLYCAEMIC DRUGS
Dr Dipti Chand
MD, IFCCM, EDIC (1)
Certificate Course in Diabetes
University of NewCastle
Ex Professor & Head
Department of Medicine
Indira Gandhi Government Medical College,
Nagpur.
Glucose Lowering Agents

2. Goals of Therapy for Type 1 or Type 2 diabetes mellitus (DM) are to
(1) Eliminate symptoms related to Hyperglycemia,
(2) Reduce or eliminate the long-term Microvascular & Macrovascular
complications of DM.
(3) Allow the patient to achieve as normal a lifestyle as possible.

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4. Glycemic control is Central to Optimal Diabetes Therapy
Comprehensive Diabetes Care of both Type 1 & Type 2
DM should also detect and manage DM-specific
complications.

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6. Depending on Etiology of DM, factors contributing to
hyperglycemia include
Reduced insulin secretion,
Decreased glucose utilization,
Increased glucose production.

7. The care of individuals with type 2 DM must also include
attention to the treatment of conditions associated with
type 2 DM (e.g., Obesity, Hypertension, Dyslipidemia,
CVD)

8. Any therapy that improves glycemic control reduces “glucose
toxicity” to beta cells and may improve endogenous insulin
secretion.
However, type 2 DM is a progressive disorder and ultimately
requires multiple therapeutic agents and often insulin in most
patients.

9. Based on their Mechanisms of Action, Glucose-lowering
Agents are subdivided into agents that
• Increase insulin secretion,
• Reduce glucose production,
• Increase insulin sensitivity,
• Enhance GLP-1 action,
• Promote urinary excretion of glucose.

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11. Insulin, produced by the beta cells of the pancreatic islets
Single-chain 86-amino-acid— preproinsulin.
Removal of the amino-terminal signal peptide —giving rise to proinsulin.
Cleavage of an internal 31-residue fragment from proinsulin
Generates C-peptide with the A (21 amino acids) and B (30 amino acids)
chains of insulin being connected by disulfide bonds.
The mature insulin molecule and C-peptide are stored together and co-
secreted from secretory granules in the beta cells.
Because C-peptide is cleared more slowly than insulin, it is a useful marker
of insulin secretion and allows discrimination of endogenous & exogenous
insulin.

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Metformin reduces fasting plasma glucose (FPG) and insulin levels,
improves the lipid profile, and promotes modest weight loss.
BIGUANIDES

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Alfa - Glucosidase Inhibitors

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Insulin Secretagogues
These drugs are most effective in individuals with type 2 DM
of relatively recent onset (<5 years) who have residual
endogenous insulin production.

19. INSULIN SECRETAGOGUES
AGENTS THAT ENHANCE GLP-1 RECEPTOR SIGNALING
“Incretins” amplify
glucose-stimulated
insulin secretion Agents
that either act as a GLP-1
receptor agonist or
enhance endogenous
GLP-1 activity.
GIP and GLP‐1 together
promote β cell
proliferation and inhibit
apoptosis

20. “Incretins” amplify glucose-stimulated insulin secretion
Agents that either act as a GLP-1 receptor agonist or enhance
endogenous GLP-1 activity are approved for the treatment of type 2 DM.
Agents in this class do not cause hypoglycemia because of the glucose-
dependent nature of incretin stimulated insulin secretion (unless there is
concomitant use of an agent that can lead to hypoglycemia sulfonylureas.
GLP-1 receptor agonists increase glucose-stimulated insulin secretion,
suppress glucagon, and slow gastric emptying.
Most patients experience modest weight loss and appetite suppression.

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Semaglutide ( S/C Ozempic, Oral - Rybelsus) treatment has been associated
with fewer CVD events and Reduced Diabetic Kidney Disease,
but with an increased rate of Retinopathy related complications
GLP-1 Receptor Agonist

22. GLP-1 receptor agonists
Short-acting GLP-1 receptor agonists are exenatide twice daily, liraglutide
daily, and lixisenatide daily.
Long-acting GLP-1 receptor agonists include sustained-release exenatide,
dulaglutide, lixisenatide, and semaglutide, all administered weekly.

23. GLP-1 receptor agonists
Daily oral semaglutide is now available that depends on gastric absorption
to avoid proteolytic degradation in the small intestine.
All are modified to avoid enzymatic inactivation by dipeptidyl peptidase IV
(DPP-IV) in the circulation.

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DPP IV - Inhibitors
DPP-IV inhibitors inhibit degradation of native GLP-1
and thus enhance the incretin effect.
Avoid these agents in patients with pancreatic disease or with other significant risk factors for acute pancreatitis
(e.g., heavy alcohol use, severely elevated serum triglycerides, hypercalcemia).

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Thiozolidinediones
Increased risk of bladder cancer.

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SGLT-2 Inhibitors
Lowers the blood glucose by selectively inhibiting
this co-transporter, which is expressed almost exclusively in the
proximal convoluted tubule in the kidney.
Euglycemic DKA may occur during illness
These agents should not be prescribed for patients with type 1 DM
or pancreatogenic forms of DM associated with insulin deficiency.

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38. THANKS