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CDSS (conversational): A diabetic case that triggered search for efficacy of teneligliptin

This case was being discussed in our group where the efficacy of teneligliptin was put under severe scrutiny and that triggered some academic searching activity among different conversational agents in the WhatsApp group: 

AS: Teneligliptin 20mg + Metformin SR 500 mg Combination is the choice of drug in what particular condition of DM??

RB: Teneligliptin is often palmed off by pharma companies to unsuspecting doctors as an oral hypoglycemic with a lower chance of hypoglycemia and even advocated in diabetics with renal failure but they hide the fact that the overall efficacy of teneligliptin is less in controlling blood sugars (as it hardly reduces blood sugars) and instead of throwing it away they are marketing it as a safe drug that doesn't cause hypoglycemia.

AS: This exactly answers precisely what I wanted to know. Thank you, Sir 🤗

As I too had a suspicion regarding its efficacy out of a personal experience with one patient (family member) who was on Glibenclamide 5mg + Metformin 500mg Combination, was asked to stop the medication by a Physician only due to her prevalent condition of often becoming hypoglycemic; sudden drop of blood sugar and also was not taking meal properly due to  condition as such Nausea + Vomiting + Abdominal Distension & Heaviness + Severe Constipation...Hence Physician asked her to stop the medication.
Still was under control for few days then it keeps rising so Another Physician started Eliptin M (Teneligliptin + Metformin) instead of Ginil-M (Glibenclamide + Metformin) as a safer alternative.

But what I found out her blood sugar is still not under control even after 10 days of Eliptin M OD before lunch meal. Though her blood sugar was quite normal and under control while she was on no medication!

AKG: How frequently you are taking recordings? Asking out of curiosity

AS: Not on a daily basis, but once or twice in a week recently when started Teneligliptin combination! Earlier once or twice in a month.

A 77 years old female
K/C/O: DM, HTN and Hypothyroidism (on Tx 75 mg) since 2004 under control. Also B/L Knee Joint Grade 3 OA with FFD in Lt Leg.

Current c/o: All complaints from 15-20 days
👉🏻 Nausea and Vomiting esp after whatever she consumes or drink
👉🏻Abdominal Heaviness & distension and also pain
👉🏻 bowel movement is not proper and unsatisfactory (Severe Constipation )
👉🏻 Difficulty in walking
👉🏻Full body pain
👉🏻 Lower backache and radiating pain from back to B/L leg (Sciatica nature of pain) due to H/O of falling down while sitting 2 months back
👉🏻 Morning stiffness
👉🏻 Tremors in both the hands

Past History: P/H

Incisional umbilical hernia following
Laparotomy for Rt Hemicolectomy for Caecal polyp, No malignancy operated in 2002

2003 - Intestinal adherent at the incisional scar carefully separated vicryl-prolene repair with prolene smooth recovery.

Appendectomy - 47 years back

Currently on Tx:

1. Thyronorm 75mg OD

2. Telimiride-H 1-0-0 (Telmisartan 40mg + Hydrochlorothiazide 12.5mg)

3. Eliptin M  0-1-0

Thereafter Started 5-day course recently 👇🏻👇🏻 as develop UTI

👉🏻 Prulifloxacin 600mg OD 0-0-1

👉🏻 Syr Uricure  (Potassium Citrate +Citric Acid)

👉🏻Cap RBSON - D (Rabeprazole 20 MG+Domperidone 30 MG)

AS: What could be the ideal thought process after witnessing such a patient ❓

Major Complaints still exist more or less 👇🏻👇🏻

Stickiness in Mouth Excessive Salivation
Anorexia
Nausea (mild improvement)
Vertigo
Constipation
Specifically, today is in hypersomnia condition and have no control and balance while standing or even sitting!!

AS: Investigation were not significant + USG only suggested Gaseous filled bowel loop

Enema Given, Stool passed, there was a lot of improvement in patient condition overall after that.

Started Ayurvedic Medicine for indigestion, Constipation, Swelling + Edema over the legs and face. Within 2 days of Ayurved medication was a significant improvement in edema + overall general condition.

Though at the time also urinary frequency was increased a lot!

On 4th day morning mild burning micturition in the morning and at night suddenly started shivering with fever (102°), BP was normal, Blood Sugar couldn't measure due to inaccessibility. (Didn't understand why this condition occurred) 🤔❓

Next Day (5th Day: 22 Aug) immediately Advised certain investigations, the same condition occurred in noontime more severely and became not oriented and unconscious thereafter mild shivering with fever and churning of teeth along with Tachypnea!! (Blood sugar was 261)

After some medication, profuse sweating took place, fever got reduced!!

Also didn't understand why this condition occurred was it due to Hyperglycemia or Septicaemia or something else 🤔❓❓
Urine R&M 24 Aug: Suggestive of UTI (does it suggest something else too 🤔❓❓) and Physician started medication mentioned above.

RB: Yes the two important differentials are hypoglycemia and sepsis to explain her intermittent symptoms. Keep us posted on her fever pattern and blood sugar pattern over the coming days.
Hope they sent the culture sensitivity before starting the antibiotics

AS: Yeah will be asking the Physician why he started Prulifloxacin ❓ didn't understand!

RB: That may be his first empirical choice (helped by the recall bias due to the pharma company rep visit just before he was about to decide)?

AS: At that time was no DM medication and earlier Glibenclamide + Metfor were stopped from 15-20 days back!! What does Neutrophilic leukocytosis with Lymphopenia (reduced from 16 to 7) suggest of in this particular patient or condition ❓

RB: Well FBS is quite high. Sepsis (in this patient due to UTI). It's a relative lymphopenia just because the neutrophils are high. And lymphopenia doesn't suggest anything other than the fact that there is neutrophilia (and so reduced slots for lymphocytes in the differential count

So to summarize drastically: 77F-->stops sugar control-->develops UTI-->put on antibiotics-->will recover 👍 But may not recover unless sugars are well controlled.

AS: 👇🏻👇🏻
15 Aug: (Before starting Eliptin M & no medication) FBS 180

22 Aug: RBS in morning 205

25 Aug: FBS 235 Eliptin M given in the morning, as u told then RBS 154 in evening
She was in drowsiness state and have no balance while standing or sitting

26 Aug: FBS 242 Today generalized stable and better than yesterday

RB: Why was it again given on 25th? 😳

RB: When was this creatinine done? Although it appears to be normal and there is no apparent contraindications for Glibenclamide please avoid using it as she has demonstrated repeated overt hypoglycemic response to this drug. Best drug in such situations would be plain insulin. Any recent repeat creatinine?

So as earlier mentioned she was on Glibenclamide 5mg + Metformin 500 mg, due to that she suffers often hypoglycemia, hence then another MD Physician started Eliptin M for 10 days and asked to monitor blood sugar it was given 0-1-0 before lunch meal.

But on that day 25 Aug, specifically Morning FBS measured on glucometer @ home was high 235 hence asked Physician to give the dose in the morning instead of the afternoon ( so it wasn't given again or 2nd dose in the afternoon, only one dose in the morning)

See her creatinine has increased from 0.87 to 1.39 and her current eGFR is 39.08 mL/min/1.73m

So only plain insulin is safe for her till her renal function normalizes. Perhaps that 0.87 creatinine earlier may have been an error?

AS: This was on 15 Aug when there were signs of edema over the leg & face, hence recommended S. Creatinine

During that & even 10-15 days back before Glibenclamide was stopped and she was on no medication!

RB: Yes this one may not have been 0.87

AS: You might be correct Sir, bcoz earlier too in another lab in another city on 11 Aug S. Creatinine was 1.31. MD Physician advised Urine Culture and USG to rule out any obstruction. For a time being Inj zostum 3 gm + 100 ml NS  iv bd.

RB: Yes her urine is suggesting a large number of pus cells so urine culture would be necessary if not done already. Even her potassium is precariously increasing

Is she on ARBs or ACEIs?

AS: Yes. Telimiride-H (Telmisartan 40mg Hydrochlorothiazide 12.5 mg) 1-0-0

Can it also be due to any Fruit juice ❓, specifically she is given pomegranate fresh juice once a day only from 2 days back?

RB: Yes both these need to be stopped

AS: So from tomorrow MD Physician advised to start GLIMISON-M1 TAB (Glimepiride 1 MG+ Metformin 500 MG ) 0-1-0. Can you pls tell how ARBs (like Telmisartan) or ACEIs responsible for this electrolytes imbalance?

Why this need to be stopped❓

RB: They cause hyperkalemia

Better not. Looks unsafe at present given her current eGFR.

AS: Ok will discuss with him then! Can you pls share more insights over that? Will also try to read some paper!

RB: If the gfr reduces any oral hypoglycemic action gets prolonged and the individual lands up in unsafe levels of hypoglycemia.

TB: Could anyone point me to comparitive efficacy data of teneligliptin? Was talking to an endocrinologist friend who said they are using teneligliptin widely in practice.

SC: Link

TB: This is placebo controlled? Any comparison with other antidiabetics? Specially other drugs of the same class?

SC: This is a good review

RB: Here's a nice placebo-controlled study from Glenmark pharma already shared above

Notice if the outcomes are clinically meaningful. "The proportion of patients who received rescue medication after 12 weeks of therapy was low and similar in both groups."

TB: Sir, I am also looking for head to head trials.

RB: As per the other review by Singh et al in 2017 there are none

SC: Small and published in not so big journal. Pio vs tene in pt already on metformin n SU

TB: Then why the switch in preference from vilda/lina to teneli

SC: Safety profile? As well as cost. This is a widely cited narrative review on the choice of gliptins..somewhat old..but u will get a fair idea.

RB: But is it cost-effective? For that matter are any of the gliptins more cost-effective than SUs?

SC: Sir..do u actually prefer SU in practice?  What is your usual 2nd drug of choice after metformin? In my case it is gliptins. Voglibose comes 3rd for me.  Don't prefer to use SU anymore...too frequent incidence of hypo...particularly among old, CKD pts..cardiac safety is challenged...obesity.

RB: We don't give SU in renal failure patients or any other patients with safety issues but for most others SU is cost effective for blood glucose control which incidentally (whatever OHAs we may choose) doesn't have much evidence to suggest root cause treatment benefits other than preventing uncontrolled hyperglycemia.

TB: Gliptins are generally being used in combination? Is that because its a known fact that the glucose lowering will be lower with gliptin monotherapy?

SC: In head to head trial b/w met+SU vs met+gliptin, probably SU scores better than gliptins as far as glycemic control is concerned. But safety profile is better for gliptins.

VP: Present study is designed with an aim to determine the effectiveness of cost-effective DPP-4 inhibitor, Teneligliptin, over the other agent of the same class.

RB: Please share the efficacy in a pico format

SC: Link. Also, Most updated Indian consensus on SU

VP: (Patients with type2dm), (Teneligliptin) vs (other agents of the same class), [no significant difference in the levels of blood sugar or glycosylated hemoglobin (HbA1c) before and after the treatment of Teneligliptin and reduced average price of INR 39 per day, when compared to other DPP-4 inhibitors.]

TB: Can we get the full text? Which other agents of the same class was compared?

VP: Full-text "Statistically, there was no significant difference between the previous DPP-4 inhibitors (Sitagliptin, Linagliptin, Vildagliptin, Saxagliptin) and Teneligliptin with respect to the level of HbA1c at a confidence interval of 95%. Teneligliptin was equally potent to any other available DPP-4 inhibitor in terms of efficacy in maintaining HbA1c.

RB: What is the significant difference between any dpp-4 inhibitor and any SU in terms of hba1c efficacy?

VP: "In matched cohorts (n = 1316/group), patients starting DPP4i, as compared with patients starting gliclazide, experienced greater reductions in HbA1c (− 0.6% versus − 0.4%; p < 0.001), fasting glucose (− 14.1 mg/dl versus − 8.8 mg/dl; p = 0.007), and body weight (− 0.4 kg versus − 0.1 kg; p = 0.006) after an average 6 months follow-up. DPP4i improved glucose control more than gliclazide, especially in patients who had failed with other glucose-lowering medications or were on basal insulin." Link 1

"There was a significantly greater reduction in HbA1c from baseline to 12 weeks with SU versus DPP4-I (MD[95% CI]=0.21%(2 mmol/mol) [0.06, 0.35]) but no significant difference at 52 and 104 weeks (MD[95% CI]=0.06%(-1 mmol/mol) [-0.03, 0.15] and 0.02%(-1 mmol/mol) [-0.13,0.18] respectively). The proportion of patients with HbA1c<7%(53 mmol/mol) without hypoglycemia was significantly higher at 52 and 104 weeks among patients on DPP4-I" Link 2

"The present meta‐analysis showed that treatment of patients with T2DM with DPP‐4 inhibitors was associated with a significantly smaller change in the HbA1c level from an intermediate time point to the end of 104 weeks of follow‐up as compared with treatment with SUs, suggesting that DPP‐4 inhibitors offer better glycaemic durability than SUs. Considering the other advantages of DPP‐4 inhibitors over SUs, such as the lower incidence of adverse events, including hypoglycaemia, and the lesser impact on body weight, the results of the present study indicate that DPP‐4 inhibitors might be a preferable treatment choice for patients with T2DM as an add‐on medication with metformin." Link 3

RB: Statistically significant but clinically not meaningful at all (at least whatever data they have gathered). The interesting thing about most studies are how the conclusions can vary between people although the results are same. Vivek you must archive this conversation around "OHA decision making" beginning with Ahmed's case presentation on tenelegliptin here as perhaps that is what I presume triggered yesterday's conversation offering further insights into how the same EBM can be utilized differently by different minimalist and maximalist camps and later this can also be published in JECP, UK. 👍


































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