Background Regular measurement of the availability and use of key medicines for non-communicable diseases allows the tracking of progress to achieve equitable access to medicines. Using a country-level public sector monitoring system for medicine supply, we aim to evaluate the availability and use of losartan 50 mg tablets and metformin 850 mg tablets between 2015 and 2020 investigating the impact of different policy changes and the COVID-19 pandemic. Methods Data from the Peruvian National System of Medicine Supply were analyzed using an interrupted time series analysis with known and unknown structural breaks. The outcomes assessed were medicine use (monthly doses dispensed at facilities over time) and medicine availability (proportion of facilities that reported having the medicine available). Results The use of losartan and metformin at the primary level of care had a linear increasing trend over the period of analysis. In secondary and tertiary levels of care, there were no increases but some significant level and trend changes of doses dispensed at different times between 2017 to 2019, but none were related to the change of procurement procedures. At all levels of care, the COVID-19 onset in April 2020 caused an abrupt drop in doses dispensed especially at the primary level. Regarding availability, we found an increasing linear trend in the primary level of care for both medicines. In secondary and tertiary levels of care, the availability fluctuated between 40 and 95%. The onset of the COVID-19 pandemic did not significantly impact medicine availability, except for losartan in the tertiary level of care. Conclusion The availability and proper dispensing of first-line medicines for hypertension and diabetes is an essential factor for sustainable and equitable treatment. Health care systems need to be prepared for forecasting the increasing demand of medicines for chronic diseases, but also to maintain effective medicine supply chains during humanitarian crisis like pandemics.